Inmunología General: Conceptos Básicos del Sistema Inmune, Universidad Europea

Universidad Europea

General inmunology Units 1, 2, 3 and 4

Organs

Basic Concepts in the Immune System

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IMMUNITY

State of protection or resistance

• Defenses against infection (what we study in microbiology)
• Microbial infection can be combated by our defenses

V There are two types of mechanisms:

1. Non-specific mechanisms
   • Non-specific or innate immunity
2. Specific mechanisms
   • Specific or acquired immunity

DEFENSE MECHANISIMS

I- NON-SPECIFIC OR INNATE IMMUNITY

• Innate Immunity: Defense mechanisms that the individual has at birth
• They do not require prior contact with the microorganism to be triggered.
• Innate defenses are always present
• They are non-specific
• Immediate response
• Independent of the "attacker" and the intensity of the aggression

II-SPECIFIC OR ACQUIRED IMMUNITY

• Specific or Adaptive Immunity
• Acquired defenses: they require prior contact with the microorganism

v Specifically recognize the microorganism

• More potent
• Stages: recognition, activation, and response
• Immunological memory

CELLS INVOLVED IN THE IMMUNE SYSTEM

PLURIPOTENT CELL(STEM CELL) MYELOID PROGENITOR PROGENITOR LINFOIDE

Erythrocyte Polymorphonuclear cells:

• Neutrophils

Megakaryocyte-platelet

• Basophils
• Eosinophils

Monocytes - Macrophages

B lymphocytes - Plasma cells

T lymphocytes:

• Helper
• Cytotoxic

Mast cells NK cells Dendritic cells

Granular leukocytes

• Granulocytes (large cytoplasmic granules, polylobed nucleus)

Neutrophils (phagocytizes bacteria - granules are digestive enzymes)

/ Basophils (important in allergic responses) V Eosinophils (active in worms and fungal infections)

• Mast cells (hypersensitivity type I. Histamine)
• Agranulocytes (very small granules, rounded nucleus)

v Monocytes (macrophages, dendritic cells) V T cells (helper and cytotoxic) V B cells (plasma cells) V Natural killer cells

CELLS INVOLVED IN THE IMMUNE SYSTEM

• Polymorphonuclear cells:
  1. Neutrophils: phagocytes.
  2. Basophils: immediate hypersensitivity type I. Histamine.
  3. Eosinophils: defense against parasites.
• Monocytes/macrophages: phagocytes.
• Mast cells: immediate hypersensitivity type I. Histamine.
• Dendritic cells: endocytosis.

> B lymphocytes: differentiate into plasma cells (antibody synthesis). > T lymphocytes: 2 types (T helper and cytotoxic T lymphocytes).

• NK cells (natural killer) = large granular lymphocytes. Lytic enzymes.

Organs of the immune system

• Primary or central lymphoid organs: (Development and maturation of lymphocytes)

✓ Thymus: T lymphocytes (They develop in the bone marrow but mature in the thymus) ✓ Bone marrow: B lymphocytes

• Secondary or peripheral lymphoid organs: (Meeting between mature lymphocytes and antigens)

✓ Spleen: defense against antigens in blood (LT and LB) ✓ Lymph nodes: interaction of circulating antigens from tissues with phagocytic cells ✓ Mucosa-associated lymphoid tissue (MALT) capture of antigens from gastrointestinal, urinary and reproductive tracts ✓ Skin-associated lymphoid tissue

Antigen

• Substance recognized as foreign by the organism
• It has two properties:
  1. Immunogenicity: the ability to provoke an immune response
  2. Antigenicity: the ability to react specifically with the products of the immune response (antibodies)

Antibodies bind to and inactivate a specific antigen.

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• Nonspecific defense mechanisms

Innate or nonspecific immune response

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Innate or nonspecific immune response

Components of the Innate or Nonspecific Response:

1. Natural Barriers: physical, mechanical, chemical, and biological These can be considered the first line of defense.
2. Mechanisms of Nonspecific or Innate Immunity: inflammation This can be considered the second line of defense.

Natural barriers

Mechanisms inherited as a part of the innate structure (1st line of defense)

V Biological barriers (normal flora, microbiota) V Chemical barriers (acidic pH stomach and vagina, lysozyme in saliva) V Physical barriers (skin and mucosal membranes) V Mechanical barriers (flicker)

Non-specific mechanisms: Inflammation

Inflammation

• Homogeneous and non-specific response
• In the event of any tissue injury:
  • Physical mechanism (wounds)
  • Chemical mechanism (irritation by abrasive)
  • Biological mechanism (allergic reaction, microorganism)
• Events:
  1. Initiation (aggression)
  2. Tissue response
  3. Leukocyte response
  4. Repair (damaged cells are replaced)

Non-specific mechanisms: Inflammation

1. Iniciation

• Presence of microorganisms or foreign molecules
• Aggression on tissues
• The organism triggers a non-specific inflammatory mechanism

2. Tissue response

• Damaged cells and microorganisms stimulate the release of chemical mediators (e.g. histamine)

Non-specific mechanisms: Inflammation

3. Leukocyte response

• Leukocyte extravasation
• Phases:
  1. Margination
  2. Rolling
  3. Adhesion
  4. Diapedesis or transmigration
  5. Chemotaxis
  6. Opsonization
  7. Phagocytosis and cell lysis

Non-specific mechanisms: Inflammation

3. Leukocyte response (continuation)

Chemotaxis: Recognition and attraction through chemical substances.

Leukocytes are guided to damaged tissue by chemotactic substances.

And they are activated by cytokines.

Non-specific mechanisms: Inflammation

3. Leukocyte response (continuation)

-Opsonization

Pathogens surround themselves with pre-existing antibodies and/or peptides of the Complement System such as C3b.

Opsonin: Substance that binds to the bacterial wall facilitating phagocytosis.

Ex: natural antibodies, Complement System proteins

Non-specific mechanisms: Inflammation

3. Leukocyte response (continuation)

-Phagocytosis and cell lysis

PUS: digestion products + dead cells + extravasated fluid

4. Reparation

Damaged cells are replaced

Non-specific mechanisms: Inflammation

CLINICAL SIGNS/SYMPTOMS OF INFLAMMATION

Redness Heat Tumor Pain

INNATE OR NONSPECIFIC IMMUNE RESPONSE

Non-specific mechanisms

Summary:

Processes involved in the Innate Response:

• Cellular factors: phagocytes and NK cells
• Inflammation
• Activation of the Complement System
• Antigen processing: Antigen-presenting cells: macrophages and dendritic cells (Langerhans cells in the skin)
• Humoral factors: cytokines

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• Humoral response

SPECIFIC, ADAPTIVE OR ACQUIRED IMMUNE RESPONSE

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SPECIFIC, ADAPTIVE OR ACQUIRED IMMUNE RESPONSE

Characteristics of specific immunity:

V It can be considered a third line of defense / They are acquired defenses v Prior contact with the microorganism v Specificity against the antigen v Specialization V Memory V Immune tolerance v Capacity to self-limit the response V Diversification of antigen recognition

SPECIFIC, ADAPTIVE OR ACQUIRED IMMUNE RESPONSE

Types of specific immune response

Humoral Immune Response

V Effectors: antibodies:

Antibodies produced by plasma cells (L-B)

• Specific binding Ac-Ag

Cellular Immune Response

V Effectors: T cells:

• Helper T cells (L-Th)L-Th:
  • L-Th: secrete cytokines

Cytotoxic T cells (L-Tc)

• L-Tc: citolysis

Both responses (cellular and humoral)occur simultaneously but sometimes one predominates over the other

SPECIFIC, ADAPTIVE OR ACQUIRED IMMUNE RESPONSE

Clonal selection theory

• Basis of the specific immune response

During their maturation, lymphocytes acquire membrane receptors

v Antigen-specific receptors Y A given antigen is presented to selected lymphocytes v Lymphocytes recognize that specific antigen v Clonal expansion of lymphocytes v Effector cells: plasma cells or plasmocytes and activated L-T cells

• Selection of B and T lymphocyte clones

SPECIFIC, ADAPTIVE OR ACQUIRED IMMUNE RESPONSE

Phases of the Specific Immune Response:

1. Recognition phase
2. Activation phase
3. Effector phase
4. Memory recovery and preservation phase

SPECIFIC, ADAPTIVE OR ACQUIRED IMMUNE RESPONSE

Phases of the Specific Immune Response:

1. Antigen recognition phase

• Each individual has a repertoire of lymphocytes
• Antigen entry
• Antigen presenting cells (APC)
• Antigen is presented to the mature virgin or naive lymphocyte
• Antigen binds to specific receptors on virgin lymphocytes

SPECIFIC, ADAPTIVE OR ACQUIRED IMMUNE RESPONSE

Phases of the Specific Immune Response:

1. Antigen recognition phase

Antigen presenting cells (APC)

Most antigens must be processed to make them recognizable by lymphocytes (L-T).

This processing makes antigens much more immunogenic (capable of triggering specific immune responses)

This task is carried out by antigen-presenting cells: macrophages, dendritic cells, L-BS

SPECIFIC, ADAPTIVE OR ACQUIRED IMMUNE RESPONSE

Phases of the Specific Immune Response:

2. Lymphocyte Activation Phase

• Proliferation of the Ag-specific lymphocyte clone.
• Lymphocytes differentiate into effector cells (they die after eliminating the Ag) and memory cells (they survive to respond to future exposure to the same Ag).
• Activated B lymphocytes transform into plasma cells or plasmacytes, secreting Abs that bind to the Ag causing its destruction.
• Activated T lymphocytes differentiate into cytotoxic cells (they directly lyse cells that present foreign proteins) and helpers that secrete cytokines.

SPECIFIC, ADAPTIVE OR ACQUIRED IMMUNE RESPONSE

Phases of the Specific Immune Response:

3. Effector phase: elimination of antigen

Activated B lymphocytes or plasma cells:

v They produce and secrete immunoglobulins into the environment. Y They are the basis of humoral immunity.

Activated T cells:

v Helper T cells (L-Th, CD4) They secrete cytokines vCytotoxic T cells (L-Tc, CD8) Lysis of cells infected by the attacking microorganism. Both branches, helper and cytotoxic, constitute cellular immunity

Innate Response - Specific Response Collaboration

• There is a very close collaboration between the innate immune response and the humoral and cellular components of the specific response. Examples:

When the APC processes the antigen, it releases proinflammatory cytokines and cytokines that activate NK cells. v Immunoglobulins promote the action of the Complement System. v Immunoglobulins are opsonins. The Ag-Ab complex enhances phagocytosis by macrophages and PMN. Helper T cells secrete cytokines that stimulate macrophages and different inflammatory processes.