Innate Immunity

Purpose of the Immune System

The purpose of the Immune system is to protect the body against pathogens (recognized via antigens) through an overlapping network of host defenses that operate on several levels

Type of Immunity barriers

Physical barriers, Immunologically active cells, chemicals

Immunity

The ability to resist damage or change from foreign substances such as microorganisms and harmful chemicals

Two type of immunity

Innate (nonspecific) & Adaptive (Specific)

Two Important Traits of Adaptive immunity

Specificity & Memory

Specificity

Ability to recognize a particular substance

Memory

Ability to remember previous encounters with a particular substance and respond rapidly

First Line of defense (Innate)

An inborn (innate), nonspecific system composed of anatomical, chemical, and genetic barriers that block microbes at the portal of entry

Second line of Defense (Innate)

Also, inborn (innate) and nonspecific and includes protective cells and fluids in tissue

Third line of Defense (adaptive)

Acquired and specific (adaptive) and is dependent on the function of T and B cells which are white blood cells called lymphocytes

Physical barriers

Prevent entry or remove microbes. Ex: skin, tears, saliva, mucous membranes, mucus. Considered the acid mantle

Chemical mediators

Promote phagocytosis and inflammation. Suface chemicals, histamine and kinins, interferons, complement, pyrogens, cytokines

Surface chemicals

Chemical mediator that lysozymes in tears and saliva

Histamine and kinins

Chemical mediators: vasodilation and increased vascular permeability during inflammation

Interferons

Chemical mediators: Viral defense proteins that protect us against viral infections and some forms of cancer

Complement

Chemical mediators: Group of 20 proteins that circulate in blood in inactive form. Promote inflammation and destroy microbes. Become activated through complement cascade

Pyrogens

Chemical mediators: Promote fever

Cytokines

Chemical mediators: Proteins secreted by cells that bind to receptors on cell surfaces, stimulating a response

Cells

Involved in phagocytosis and production of chemicals

Activated complement proteins can:

• Form membrane attack complex (MAC): Make channel through plasma membrane of microbe resulting in cell lysis

• Trigger opsonization: complement proteins can attach to surface of bacterial cells, stimulating phagocytosis via WBC

• Cause Chemotaxis: attract immune system cells to the site of infection and promote inflammation

Compliment Cascade

1. The classical pathway begins when an antigen–antibody complex binds to C1. The C1-antigen-antibody complex activates C4.

2. Activated C4 binds with C2 and activates C3, triggering the complement cascade via the classical pathway

3. The alternative pathway begins when C3 is spontaneously activated. If activated C3 does not interact with a microorganism, it is quickly inactivated by proteins on the surface of the body’s cells.

4. Activated C3 can become stabilized by combining with some foreign substances, such as part of a bacterial cell or virus.

5. Once C3 is stabilized by either pathway, it stimulates the complement cascade by activating C5 -> C6 -> C7 -> C8 -> C9

6. Activated C3–C7 promote phagocytosis, inflammation, and chemotaxis (attracts cells).

7. Activated C5–C9 combine to form a membrane attack complex (M A C). 

Alternative Pathway

Part of Innate Immunity: C3 binds with foreign substance. Attracts macrophages and eventually lyses the cell. Activates spontaneously and older

Classical Pathway

Part of adaptive immunity. Requires antibodies bound to antigens

Can virus infected cells be saved?

Virus infected cells can produce interferons. These can’t save the infected cell, but can signal to neighboring cells and stimulate them to produce antiviral proteins that will stop viral replications in the neighboring cells

White blood cells

Most important cellular components of immune system. Self vs. non-self

Chemotaxis

Movement toward the source of chemotactic factors (parts of microbes or chemicals act as chemical signals and attract WBCs)

Phagocytosis

Endocytosis and destruction by phagocytes (neutrophils and macrophages

Neutrophils

·       Phagocytic and first cells to enter infected tissue: only last a few hours

·       Release chemical signals that increase the inflammatory response by recruiting and activating other immune cells

·       Also release lysosomal enzymes that kill microorganisms and cause tissue damage; may produce pus

·      Regularly cross wall of gastrointestinal tract, providing protection

Macrophages

·       Large phagocytic cells. Monocytes that leave blood and enter tissues. Longer-lived than neutrophils, can ingest larger particles

·       Produce a variety of chemicals such as interferons, prostaglandins, and complement

·       Found beneath free surfaces such as the skin, subcutaneous tissue, mucous membranes, and serous membranes

·      May have different names in different tissues; reticuloendothelial cells in sinuses, dust cells in lungs, Kuppfer cells in liver, microglia in CNS…

Basophils and Mast Cells

·       Promote inflammation when activated by innate or adaptive system, release histamine

·       Basophils are motile, leave blood and enter infected tissues

·      Mast cells are non-motile; in C.T.

Eosinophils

·      Leave blood and enter tissues  

·      Reduce inflammation by breaking down chemicals produced by basophils and mast cells

·      Secrete enzymes that kill some parasites

Natural Killer Cells

·      Type of lymphocyte that Lyse tumor and virus-infected cells

·      Recognize whole classes of cells, not specific kind of cell

Example of Inflammatory Response

§  1. Splinter damages tissue allowing bacteria to invade which causes more tissue damage

§  2. Chemical mediators are released

§  3. Chemotaxis, increased vascular permeability causing edema, increased blood flow causing redness

§  4. Increased numbers of white blood cells and chemical mediators at site of tissue damage

§  5. Bacteria are contained, destroyed, and phagocytized

§  6. Bacteria either are destroyed or remain

§  7. If bacteria destroyed tissue repair occurs but if not additional chemical mediators are activated, and the process repeats from step 2.

Tissue injury can cause

Inflammation

Inflammation

The bodies local response to injury. Response initiated by chemical mediators that trigger vasodilation, chemotactic attraction, and increased vascular permeability. The latter allows fibrinogen and complement to enter tissue. Fibrinogen converted to fibrin, walls off infected area

Local Inflammation

Confined to a specific area of the body. Symptoms are redness, heat, swelling, pain, loss of function

Systemic Inflammation

Occurs in many parts of the body

Systemic inflammation has the same symptoms as local in addition with:

§  Increase in neutrophil numbers released by red bone marrow

§  Fever due to production of pyrogens by various kinds of cells. Improves performance of immune system – signals for hypothalamus to raise body temp and muscles to increase heat production

§  In severe cases, get widespread increased vascular permeability due to histamines. Large volume of plasma enters interstitial spaces leading to shock/death