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Summary - Prevention 1 - Immunological basis of vaccination
What is vaccination?
Vaccination is an intervention to provoke a beneficial immune response without getting the disease.
2 Immune response
- ANTIGEN RECOGNITION: Ag presentation to lymphocytes (T and B lymphocytes) by dendritic cells (occurs in lymphoid tissues)
- LYMPHOCYTE ACTIVATION: Proliferation and differentiation of activated T and B lymphocytes ( lymphoid tissues)
- ANTIGEN ELIMINATION: Lymphocyte effector functions at the site of inflammation (humoral/cell-mediated immunity)
- CONTRACTION (homeostasis): Abortion of effector T and B lymphocyte clones (by Ag deprivation)
- MEMORY: Formation of T and B memory cells (lymphoid tissues)
Immune response - description
The Immune Response
An immune response is initiated when the body's immune system recognizes the presence of a pathogenic organism, or other foreign material, that has managed to break through the body's physical and chemical barriers to infection.
There are two branches to an immune response:
Each of these is carried out by a distinct set of immune cells that are derived in the bone marrow from hematopoietic stem cells. The cells of the innate and adaptive immune cells are sometimes referred to as white blood cells or leukocytes (leuko: Greek meaning white). This name derives from their color as can be seen in the accompanying figure.
Two major lineages of white blood cells exist.
- The myeloid lineage, which gives rise to effector cells of the innate immune response (monocytes, macrophages, neutrophils and dendritic cells)
- The lymphoid lineage, which gives rise to effector cells of the adaptive immune response (T cells and B cells, also known as T lymphocytes and B lymphocytes)
The myeloid and lymphoid lineages are illustrated in the figure below.
The innate immune response is the first line of defense initiated against and invading pathogen. The innate response is a generalized type of response that recognizes and responses to broad classes of microbes. If an innate response is not able to rid of an invading pathogen, an adaptive immune response will be generated against the pathogen. The adaptive response, which generally peaks 4-7 days after the onset of first infection, is a more versatile response than the innate response; it is a very specific response that will only be directed against the specific invading pathogen.
As an example, consider the case of an immune response that occurs as a consequence of infection with a specific strain of influenza. Initially, the innate immune system will recognize in a very general way that there is an infecting virus, and it will mount a somewhat generic anti-viral response, that will be slightly different from the response it would mount against a parasitic worm. If the innate response is unable to resolve the infection, the subsequent adaptive immune response that is generated will only be targeted against influenza virus and, in particular, the specific strain of infecting influenza virus, and it will not recognize any other virus type.
2.1 INNATE IMMUNE SYSTEM
INNATE IMMUNE SYSTEM
- non-specific response
- first line of defense --> immediate defense against infection, exposure leads to immediate maximal response
- CELL-MEDIATED and HUMORAL components
- no immunological memory
- INFLAMMATION: Recruiting immune cells to sites of infection, through the production of chemical factors, including specialized chemical mediators, called cytokines.
The process of acute inflammation is initiated by cells already present in all tissues, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mastocytes. These cells present on their surfaces certain receptors named pattern recognition receptors (PRRs), which recognise molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). At the onset of an infection, burn, or other injuries, these cells undergo activation (one of their PRR recognize a PAMP) and release inflammatory mediatorsresponsible for the clinical signs of inflammation.Chemical factors produced during inflammation (histamine, bradykinin,serotonin, leukotrienes, and prostaglandins) sensitize pain receptors, causevasodilation of the blood vessels at the scene, and attract phagocytes, especially neutrophils. Neutrophils then trigger other parts of the immune system by releasing factors that summon other leukocytes and lymphocytes.Cytokines produced by macrophages and other cells of the innate immune system mediate the inflammatory response. These cytokines include TNF,HMGB1, and IL-1.
- COMPLEMENT SYSTEM: Activation of the complement cascade to identify bacteria, activate cells and to promote clearance of dead cells or antibody complexes.
The complement system is a biochemical cascade of the immune system that helps, or “complements”, the ability of antibodies to clear pathogens or mark them for destruction by other cells. The cascade is composed of many plasma proteins, synthesised in the liver, primarily by hepatocytes. The proteins work together to:
-> trigger the recruitment of inflammatory cells.
-> "tag" pathogens for destruction by other cells by opsonizing, or coating, the surface of the pathogen.
-> forming holes in the plasma membrane of the pathogen, resulting incytolysis of the pathogen cell, causing the death of the pathogen.
-> rid the body of neutralised antigen-antibody complexes.
- CELLS OF THE INNATE IMMUNE SYSTEM: The identification and removal of foreign substances present in organs, tissues, the blood and lymph, by specialised white blood cells.
- MAST CELLS
- PHAGOCYTES: macrophages, neutrophils and dendritic cells
- BASOPHILS and EOSINOPHILS
- NATURAL KILLER CELLS
- Acting as a physical and chemical barrier to infectious agents.
Recognition --> Response
Macrophages and immature dendritic cells (sometimes referred to as "antigen-presenting cells") are effector cells of the innate immune response. These cells reside in peripheral tissues where they act as sentinels, ready to respond when an organism (or other foreign, non-self material) breaches the body's nonspecific barriers to infection. When a pathogen does break through a barrier such as the skin, the macrophage and immature dendritic cells will recognize its presence through pathogen recognition receptors, including the Toll-like Receptors (TLRs). Pathogen stimulation of TLRs results in activation of innate immune cells and initiation of the innate response.
Upon activation macrophages provide a first line of immune defense against the infecting pathogen in several ways. One of the major macrophage functions is to engulf(phagocytize) and kill the invading microorganism. Another important function is to release small signaling proteins, cytokines and chemokines that help to promoteinflammation by, in part, activating and recruiting other innate immune cells into the immune response. Macrophage-secreted cytokines function to increase the permeability of blood vessels to fluid and protein. Chemokines released by macrophages act as chemoattractants that direct the migration of additional types of immune cells, neutrophilsand monocytes from the blood to the site of infection in the peripheral tissue. Neutrophils are the most abundant and most important cells of the early innate response, primarily due to their role in phagocytizing and destroying invading microorganisms. Recruited monocytes differentiate into macrophages that also aid in fighting the infection.
Together, neutrophils and macrophages are the main effector cells of the inflammatory process that is the hallmark of an innate immune response.