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Internal defenses: secondary barriers

If the external barriers are overcome, a second system of internal barriers operates. It can be divided into two types:

These secondary barriers constitute the innate immune system, present in all living beings, nonspecific, fast-responding and lacking immunological memory.

Components of secondary defensive barriers

The second defense barrier is composed of two types of nonspecific components: cellular and molecular.

Nonspecific cellular components:

The cells that are part of this secondary barrier are:

  • Granulocytes (or polymorphonuclear leukocytes): a type of leukocytes (white blood cells) characterized by having numerous granules in the cytoplasm. There are three types of granulocytes:
    • Neutrophils.
    • Eosinophils.
    • Basophils.
  • Monocytes: They are a type of agranulocyte white blood cells that circulate in the bloodstream and go to injured tissues, where they become  macrophages, which engulf the pathogen and act as antigen-presenting cells.
  • Mast cells: cells of the connective tissue that contain granules of histamine and heparin. They intervene in inflammatory and allergic processes.
  • NK or Natural Killer cells. They are a type of lymphocyte that is responsible for destroying cells infected by viruses, cancer cells, and cells from transplanted organs. They are not phagocytic cells.

Linaje de las células sanguíneas

Arcadian - Traducido por MatNet [Dominio público Dominio], via Wikimedia Commons

Nonspecific molecular components:

There are also other nonspecific molecular components of this secondary defensive barrier, which are dissolved in blood plasma:

  • Interferon: is a set of proteins produced by cells that have been infected by a virus, bacteria, parasites and tumor cells. It intervenes in a nonspecific and specific way.
    • It activates defenses in nearby cells, activating NK cells and macrophages and increasing antigen presentation, since it increases the expression of the major histocompatibility complex (MHC) antigens.
    • If the cell is infected by a virus, they bind to receptors on the membrane of the infected cell, preventing the virus from replicating. In addition, it increases the resistance of healthy cells to virus infection.
  • Complement system: It is a set of plasma proteins produced in the liver, whose direct function is the recognition and destruction of pathogens when they invade our body. If there are no antigens, these proteins are inactive. But the presence of molecules on the bacterial surface or of antigens attached to antibodies, causes a biochemical cascade activation, in which some proteins activate others. Complement activation is done in two ways:
    • Classic pathway: it is part of the adaptive immune response, so it is a specific type of defense. It is activated when antibodies bind to antigens that coat the surface of pathogenic microorganisms.
    • Alternative pathway: it is part of the innate immune response. It is a type of nonspecific defense. It is produced by the presence of foreign structures in the microbial cell envelopes. It is independent of the antigen-antibody complexes

Complement activation facilitates: 

- The action of phagocytes through opsonization.

- The lysis of pathogenic cells.

- The generation of the inflammatory response, stimulating mast cells to release histamine. It is a mediator of inflammation.

  • Cytokines. They are proteins that regulate the function of the cells that produce them on other cell types. They regulate, coordinate and enhance the immune response. For example, interleukins, synthesized by leukocytes, which induce their growth and differentiation. Another example would be interferons.

Nonspecific internal defense mechanisms

If pathogenic microorganisms or any other foreign substance overcome the primary defensive barriers  and reach the interior, the internal components (cells and molecules) begin to act in two ways:


If the pathogen overcomes the primary barriers, they encounter phagocytes, a type of leukocytes that form the second defensive barrier.

The phagocytes are cells with phagocytic capacity Nonspecific that by pseudopodia, encompass microorganisms and useless cells, forming a phagosome, digesting them after their lysosomes.

There are two different types of phagocytes:

  • The microphagous or leukocytes Neutrophils are the most abundant phagocytes. They reach the place where the diapédesis infection has occurred, through the walls of the blood capillaries until they reach the tissues and engulf the pathogenic microorganisms. 
  • The monocyte, a type of leukocyte that after spending several days in the blood, move to different tissues (of the liver, spleen, lungs, bone marrow, ...) and transformed macrophages larger cells, and greater phagocytic capacity. Macrophages can move or remain fixed (if they remain fixed they are called histiocytes). Macrophages are the main constituents of the reticuloendothelial system.

Inflammatory response

When a wound occurs (or by any antigen), the skin breaks and microorganisms can enter the interior of the body. The cells secrete substances that mediate inflammation inflammation (such as histamine and serotonin produced by basophils and mast cells) that provoke the inflammatory response by attracting cells such as phagocytes (macrophages or neutrophils), consisting of:

  • Capillary vasodilation: more blood arrives. They produce an increase in temperature and blush.
  • Greater permeability of blood capillaries, favoring diapédesis, allowing the exit of more plasma and blood cells. It produces swelling and pain. 
  • Migration and activation of phagocytes: Vasodilation and increased permeability of capillaries allows more phagocytes to access the area, which produces phagocytosis and opsonization.
  • Pus formation. As germs engulf, many phagocytes die forming "pus". The pus is a thick liquid of yellowish or whitish color formed by a mixture of blood serum, dead bacteria and white blood cells dead after phagocytose large amounts of bacteria, injured cells and foreign substances.

This inflammatory response causes an increase in temperature in that area, redness, swelling and pain, due to the excitation of the nerve endings. Its purpose is to isolate and inactivate pathogens and restore damaged areas.

When the infection is strong, pyrogenic substances are produced that increase body temperature causing fever, favoring the displacement of leukocytes and making it difficult for bacteria to develop, as they are at a temperature higher than the optimum for their development.

The main characteristics of inflammation are:

  • Tumor (Swelling). Interstitial fluid increases and edema forms.
  • Rubor. Redness produced by vasodilation.
  • Heat. Vasodilation and local oxygen consumption produces an increase in the temperature of the inflamed area. 
  • Pain. It appears as a consequence of the release of substances capable of causing the activation of nociceptors, such as prostaglandins.
  • Loss or decrease of function.

Questions that have come out in University entrance exams (Selectividad, EBAU, EvAU)

Madrid, July 2020, question A4

A.4.- (2 points) In relation to the immune response:

a) What is interferon and what is it for? (0.5 points).
b) State what you mean by opsonization and name two types of molecules capable of carrying it out (0.75 points).
c) What does it mean that a cell has cytotoxic activity? Give two examples of cells that have this activity (0.75 points)

Madrid, July 2018, option A, question 5.

In relation to the body's response to a wound.

a) Define inflammation (0.5 points).

b) Name four characteristic symptoms of the inflammatory response (0.5 points).

c) Define mediator of inflammation and name three of them (1 point).

Andalusia, June 2019, option B, question 3 .

a) Define the inflammatory response  [0.5] and 

b) Indicate its purpose. [0.5]

c) Cite the name of a cell and a molecule involved in the inflammatory response [0,4].

d) List three characteristic symptoms of the inflammatory response [0.6].

Extremadura, June 2019, option B, question 5

Describes the role of mucous membranes as a defensive barrier against infections (1 point)

Extremadura, July 2019, option B, question 5, section A

Briefly describe the inflammatory reaction as a defensive response to a pathogen. (1 point)

La Rioja, July 2020, question 19

When a foreign agent, such as the SARS-CoV-2 virus, manages to penetrate the interior of a person, various defense mechanisms are activated. Explain the nonspecific mechanisms that respond to virus invasion.


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