MICR 270 Module 2: Branches of the Immune System

MICR 270 Module 2 Flashcards

Innate Immune System

The first line of defense. Non-specific and relies on pattern recognition. Responds to all pathogens the same way. Comprised of immune barriers, pattern recognition, inflammation, and phagocytosis.

Physical Barriers

Skin: Largest organ.

Mucous Membrane: cilia and mucous covers body cavities to trap and sweep away pathogens.

Chemical Barriers: Tears and saliva contain antimicrobial substances like lysozyme. Gastric acid in the digestive tract.

Cellular Barriers

Neutrophils

Macrophages

Dendritic Cells

NK cells

Components of the Soluble Barrier

The Complement System

Cytokines

The Complement System

>30 soluble proteins that complements the efficiency of other systems. (Inflammation, Phagocytosis, MAC)

Complement system activation.

Three pathways: Classical, Lectin, Alternative. Activated through signaling cascades and forms the membrane attack complex (MAC).

Inflammation and the Complement System

Complement proteins bind complement receptors on immune cells signaling the release of chemotactic factors. Chemotactic molecules attract immune cells to the site of infection.

Phagocytosis and the Complement System

C3b proteins mark pathogens to be phagocytosed (opsonization).

The Membrane Attack Complex

Destroys extracellular invaders and creates holes in pathogens leading to cell lysis and death. A deficiency in the complement system would lead to longer periods of infection.

Cytokines

Proteins that are secreted by immune cells that have affinity for cytokine receptors. They act through autocrine and paracrine signaling and by binding to receptors, they induce changes in gene expression. Pro-inflammatory cytokines and anti-inflammatory cytokines maintain equilibrium in the body.

Signs of the Inflammatory Response

Pain, Redness, Swelling, Heat, Loss of Function.

Steps of the Inflammatory Response

1. Breech

2. Vasodilation

3. Permeabilization

4. Extravasation

5. Phagocytosis

Breech (1)

Pathogen crosses physical barriers and enters the body (injury)

Vasodilation (2)

Vessels increase in diameter and permeability through vasoactive and chemotactic molecules. responsible for redness and heat.

Permeabilization (3)

Capillary permeability increases followed by vasoconstriction of the surrounding area. Exudate (filled with complement proteins and pro-inflammatory cytokines) builds up forming an edema. The accumulation of fluid causes swelling.

Extravasation (4)

Immune cells are recruited by chemotaxis. Neutrophils attach to epithelial cell walls (margination) then migrate into the tissue at the site of infection (diapedesis)

Phagocytosis (5)

Phagocytes engulf pathogens. If the infection persists, the adaptive immune system is engaged.

Pattern Recognition Receptors

Recognize repeated patterns in pathogens to initiate the innate immune response. Many families exist.

PAMPs

Pathogen Associated Molecular Patterns. Are expressed on the cell surface or the surface or interior. The patterns are specific to each pathogen and different molecules are indicative of different groups.

DAMPs

Danger/Damage Associated Molecular Patterns. Are released by cells undergoing necrosis. Indicate damage to the host cell. Can include molecules in places they are not supposed to be (DNA outside the cell).

TLRs

Toll-like receptors. A class of PRR that is expressed on the plasma membrane of the endosomal/lysosomal membrane. They induce the transcription of pro-inflammatory cytokines, chemokines and costimulatory molecules when activated. They increase phagocytic ability.

TLR activation process

1. DAMP/PAMP mediated activation

2. Antigen presented via MHC

3. Costimulatory molecules enhance and stabilize the antigen presentation

4. Naive T-cells bind MHC via TCRs

Phagocytosis Steps (5)

1. Attachment

   Pathogen attaches to pseudopodia

2. Ingestion

   pathogen is ingested, a vacuole is formed

3. Fusion

   Vacuole fuses with a lysosome and macromolecule + bacteria are degraded

4. Digestion

   Pathogen is digested by lysosomal enzymes

5. Release

   The digested products are released via exocytosis

Adaptive Immunity

The second line of defense. Includes specific and diverse responses.

Cells of Adaptive Immunity

B cells

• humoral immunity

T cells

• Cell mediated immunity

Antigen Presenting Cells

APCs present antigens to T_H causing them to differentiate into T_H1 or T_H2 . TH1 is cell mediated and activates CTLs that will eliminate cells displaying the antigen in their MHC class I. TH2 activates B cells triggering their differentiation into plasmacytes.

Antibodies

“Immunoglobulins”. Are “Y” shaped proteins that are specific to a singular epitope. They are responsible for:

• Neutralization

• Opsonization

• Complement Activation

• Effector Cell Activation

Surface antibodies vs. soluble antibodies

Surface antibodies are membrane bound to B cells. Soluble antibodies circulate in the blood and are secreted by plasmacytes.

Antibody structure

Light Chain

Heavy Chain

Antigen Binding Region (variable)

Fc Region (constant, binds to Fc receptors)

Antibody Classes (5)

IgM

IgA

IgG

IgE

IgD

IgM

Pentamer, activates the complement, the first antibody formed.

IgA

Dimer, found in mucosal membranes, the first line of defense.

IgG

Monomer, opsonization by coating pathogens, can cross the placental barrier.

IgE

Monomer, involved in allergic reaction and parasite immunity.

IgD

Monomer, found on the surface of B cells in large quantities, not really sure what it does…