Lecture 1: Introduction to Immunology

Key Points:

Video's of Phagocytocysis

Phagocytosis of E. coli
Attempt at phagocytosis of Streptococcus
(Movies from James A. Sullivan, CellsAlive!, Charlottesville, Va, USA)

The defense of a host towards foreign bodies can be divided into Innate Immunity and Acquired Immunity.

Innate immunity is present continuously, it is a defense mechanism that is present from birth.

Acquired immunity is induced by the presence of foreign material and is usually quite specific. The fundamental properties of acquired immunity are:

  1. Specificity
  2. Adaptiveness
  3. Discrimination between self and non-self
  4. Memory

1. Innate Immunity:

1.1 Physical Barriers:

1.2 Physiological Barriers:

1.3 Cellular Barriers:

 

Cellular Fate of Ingested Material:

1.4 Direct Cellular Killing: Natural-killer (NK) cells are lymphocytes that can recognize and destroy viral or cancerous cells. NK cells contact other cells. If the other cell appears to be abnormal (i.e. virally infected or cancerous) then the NK cell releases cytotoxic molecules that cause the abnormal cell to undergo apoptosis. NK cells respond to levels of class I MHC (major histocompatibility antigen) molecules on cell surface. Reduced levels in viral and cancerous cells result in killing.

Apoptosis-programmed cell death without release of cellular contents.

1.5 Inflammatory Response: This is an important response to cellular injury or infection. It has both a rapid innate phase as well as a prolonged phase that is an important component of acquired immunity.

Immediately after injury or infection a number of proteins are released. These lead to the physiological characteristics of inflammation: swelling, redness, heat, and last but not least, pain.

Acute phase proteins that are released are:

kinins

  • cause contraction of muscles distal to the site, causing blood to back-up at the affected site,
 
  • cause vascular cells to contract and to express endothelial adhesion molecules. These allow cells in the blood stream to first attach to the capillaries and then enter the affected site,

  • simulate nerves, leading to pain.

Cytokines

  • induce adhesion molecules,

  • increase vascular permeability,

  • attract leukocytes.

C-reactive protein

  • Primes certain bacteria for destruction by the complement system.

 

The three major cytokines released from tissue macrophages are IL-1 (interleukin 1), TNF-a , IL-6. The roles of these proteins in the inflammatory response are listed below (from Kuby):

Effect

IL-1

TNF-a

IL-6

    • Increased vascular permeability

+

+

+

    • Increased adhesion molecules on endothelium

+

+

-

Acute-phase response

     
    • Platelet production

+

-

+

    • Induce fever via hypothalamus

+

+

+

    • Induce production of acute phase proteins:

C-reactive protein, fibrinogen (blood clotting)

+

+

+

    • T and B cell activation

+

+

+

    • Increased immunoglobulin synthesis

-

-

+

If the response persists for more than a few hours then macrophages and lymphocytes are recruited to the site. These cells aid in phagocytotic activity. Macrophages also are involved in presentation of foreign peptides to cells of the acquired immunity system, initiating the formation of antibodies against the infectious agent.