The Immune System

Leucocytes

Lymphatic system

INNATE IMMUNITY

• The innate immunity system is what we are born with and it is nonspecific; all antigens are attacked pretty much equally. It is genetically based and we pass it on to our offspring.

Surface Barriers or Mucosal Immunity

1.The first and most important barrier is the skin. The skin cannot be penetrated by most organisms unless it already has an opening, such as a nick, scratch, or cut.

2. Pathogens are expelled from the lungs by ciliary action as the tiny hairs move in an upward motion; coughing and sneezing abruptly eject both living and nonliving things from the respiratory system; the flushing action of tears, saliva, and urine also force out pathogens, as does the sloughing off of skin.

3. Sticky mucus in respiratory and gastrointestinal tracts traps many microorganisms.

4. Acid pH (< 7.0) of skin secretions inhibits bacterial growth. Hair follicles secrete sebum (contains lactic acid and fatty acids) that inhibit the growth of some pathogenic bacteria and fungi. Areas of the skin not covered with hair, such as the palms and soles of the feet, are most susceptible to fungal infections. (Think athlete's foot.)

5. Saliva, tears, nasal secretions, and perspiration contain lysozyme, an enzyme that destroys bacterial cell walls causing cell lysis. Vaginal secretions are also slightly acidic. Spermine and zinc in semen destroy some pathogens.

6. The stomach is a formidable obstacle insofar as it secretes hydrochloric acid (0.9 < pH < 3.0, very acidic) and protein-digesting enzymes that kill many pathogens. The stomach can even destroy drugs and other chemicals.

Inflammatory Response

• The inflammatory response occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause.

• Chemicals, such as histamine, bradykinin and serotonin, are released by damaged tissue. These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. This helps isolate the foreign substance from further contact with body tissues.

• Interleukin is one of the most important chemicals. It stimulates lymphocytes and other white blood cells into action.It also promotes fever by resetting the body's thermostat located in the hypothalamus.

• The chemicals also attract white blood cells that "eat" microorganisms and dead or damaged cells. The process in which these white blood cells surround, engulf, and destroy foreign substances is called phagocytosis, and the cells are called phagocytes. Phagocytes eventually die. Pus is formed from a collection of dead tissue, dead bacteria, and live and dead phagocytes.

Summary of the inflammatory response• Entry of microbes (i.e. bacteria). • Vasodilation of the microcirculation (small blood

vessels) resulting in increased blood flow. • An increase in vascular permeability to protein. • Filtration of fluid into the tissue which leads to

swelling. • Neutrophils (a type of white blood cell) and later

monocytes (another type of white blood cell) migrate from the blood vessels into the tissues.

• Phagocytosis and destruction of the microbes. • Tissue repair.

Complement Response

• Complement is a group of serum proteins which work with (complement) antibody activity to eliminate pathogens.

• Complement is NOT antigen-specific and it is activated immediately in the presence of pathogen, so it is considered part of innate immunity.

• However, antibody activates some complement proteins, so complement activation is also part of humoral immunity.

• Complement proteins are present in the circulation as inactive molecules.

• Several complement proteins are pro-enzymes. When activated, they become proteases that cut peptide bonds in other complement proteins to activate them in turn.

• Since each activated protease can activate many substrate molecules, the initial activation is rapidly amplified to produce millions of activated molecules (a cascade).

Complement activation stimulates several antimicrobial activities:

1. One activity is the formation of a membrane attack complex (MAC), which inserts into lipid membranes of bacteria or eukaryotic cells and causes osmotic lysis.

2. Complement fragments called opsonins adhere to microorganisms and promote phagocytosis, and activation of macrophage and neutrophil killing mechanisms.

3. Complement fragments called anaphylatoxins promote an inflammatory response by binding to complement receptors on mast cells and triggering release of histamine, which increases blood vessel permeability and smooth muscle contraction.

A little quiz1. Complement a. is a group of active proteolytic enzymes

found in serum. b. is secreted by macrophages and

hepatocytes in response to antigen binding.c. participates in both innate and adaptive

immune responses.d. prevents lysis of virus-infected cells. e. all of the above statements about

complement are true.

2. Complement is involved in all of the following except

a. attraction of neutrophils to an infection site.

b. increased presence of serum proteins in the infected tissues.

c. lysis of bacteria in the absence of specific antibodies.

d. opsonization of microorganisms for phagocytosis.

e. sensitization of T cells to antigen

3. Complement is

a. activated by binding to specific complement receptors.

b. antigen-specific.

c. a potent promoter of virus entry into host cells.

d. a series of intracellular proteins which work with antibody to eliminate endogenous antigen.

e. present in the circulation in an inactive form. Answers are at the end of the

pp

SPECIFIC IMMUNITY• Specific immunity, also known as adaptive

immunity, normally comes into play when innate or non-specific immunity can't handle the problem.

• This form of immunity is a more recent evolutionary development than innate

• It is distinguished by its specificity for an invading organism and for its ability to remember (anamnesis) an encounter so that the second time the same organism or invader is encountered a more rapid and intense response can occur.

• There are two types of specific immune responses: humoral and cell mediated.

• Humoral immunity is mediated by B Lymphocytes that produce antibodies (IgG, IgM, IgA, IgE) and is especially important in combating acute bacterial infections.

• Cellular immunity is mediated by T Lymphocytes which are processed in the thymus. Cellular immunity is especially important in combating intracellular organisms such as TB, performing tumor surveillance, mediating transplant rejection, and fighting fungal and viral infections.

Cell mediated immunityT Cells: have two major roles in immune

defense. 1. Regulatory T cells are essential for directing

and organizing the response of different types of immune cells. – Helper T cells (aka CD4 cells)

• Alert B cells to start making antibodies; • Activate other T cells• Activate macrophages• Influence which type of antibody is produced.

2. Killer T Cells destroy infected cells

Killer T cells (aka CD8 cells):– attack and destroy infected cells by lysis.– The killer T cells are also called cytotoxic T

cells.

Activation of helper T cells

                                               

   After it engulfs and processes an antigen, the macrophage displays the antigen fragments combined with a Class II MHC protein on the macrophage cell surface. The antigen-protein combination attracts a helper T cell, and promotes its activation.

                                           

              

After a macrophage engulfs and processes an antigen, the macrophage displays the antigen fragments combined with a Class I MHC protein on the macrophage cell surface. A receptor on a circulating, resting killer T cell recognizes the antigen-protein complex and binds to it. The binding process and a helper T cell activate the killer T cell so that it can attack and destroy the diseased cell.

Activation of killer T cells

Humoral immunity

• B cells produce antibodies that circulate in the blood and lymph streams and attach to foreign antigens to mark them for destruction by other immune cells.

• B cells are part of what is known as antibody-mediated or humoral immunity

Activation of B cells to make antibody

                                 

          

A B cell uses one of its receptors to bind to its matching antigen, which the B cell engulfs and processes. The B cell then displays a piece of the antigen, bound to a Class II MHC protein, on the cell surface. This whole complex then binds to an activated helper T cell. This binding process stimulates the transformation of the B cell into an antibody-secreting plasma cell.

                            

Antibody formation by B cells

B cells become plasma cells, which produce antibodies when a foreign antigen triggers the immune response.

Go to this site

• http://www.biologymad.com/

and click on Immunology

The explanations are clear, concise, and the illustrations are great!

Answers to “A little quiz”

1. C 2. E 3. E