BASICS - INNATE & ACQUIRED

INNATE

• The acquired immune system is a specific response to a certain pathogen and  is principally brought

   about by T-cells, B-cells, immunoglobulin and complement. 

https://www.aagbi.org/sites/default/files/323%20Immunology%20for%20Anaesthetists%20Part%201%20-%20Basic%20Immunology.pdf

@Gas_Craic

• The innate immune response is non- specific & destroys pathogens mainly through
   phagocytosis + activation of complement

"The immune system is a complex network of cells and proteins that are able to protect against infection. The innate response is largely brought about by phagocytes and complement proteins whereas the acquired system relies on a more specialised cellular and humoral response bought about by T and B-cells. The two systems are closely interlinked and work synergistically to assist in fighting foreign invaders."

ACQUIRED

• Describes responses to infection that have been ‘learnt’ by the immune system over time.
  
• Innate immunity has to work in unison with specialised cells of the acquired system.
  
• Following primary pathogenic exposure, the acquired response takes time to develop.
  
• Memory in this system gives subsequent infections with the same pathogen lead to a rapid response - think vaccines.
  
• Acquired = ‘humoral' component brought about by B-cells and a cellular component brought about by T-cells.
  
• As lymphocytes, these cells both mature from haemopoietic stem cells in the bone marrow but are sub-classified according to their site of differentiation;
  T-cells develop in the thymus, whereas B-cells develop in bone marrow.
  
• T and B cells express highly specific cell surface receptors. The mammalian genome codes for millions of different T and B cell receptors.
  
• During development, cells are selected for the ability of these receptors to recognise specific antigens. Importantly, any cell that responds strongly to ‘self’ proteins are deleted to prevent immune attack on the body’s own cells; this is a process that may be defective in auto-immune diseases.
  
• Cells that respond strongly to non-self peptides then remain ‘naïve’ until they are activated during future infection in secondary lymphoid tissues of the spleen, lymph nodes or mucosa-associated lymphoid tissue (MALT).
  

Complement

• Liver produces complement proteins that are involved in both innate and acquired immunity.
  
• Chain of events is activated by microbial invasion & a process called the complement cascade.
  
• The 2 main ways the complement system destroys microbes; opsonisation & complement cascade.
  
• Opsonisation = the labelling of foreign pathogens by complement proteins —> macrophages & phagocytosis.
• Binding of complement proteins also leads to the activation of the complement cascade.
• This is a more complex process of protein activation which directly induces microbial death by making a membrane attack complex. 
• This complex effectively ‘punches a hole’ to disrupt the cell wall and kill the microbe.
• The complement cascade can be activated by three pathways; classical, lectin and alternative.
• All lead to the hydrolysis of complement protein C3 into C3a and C3b.C3a acts as an inflammatory cytokine whilst C3b acts as an opsonin or initiator of the membrane attack pathway.
• Complement proteins C3a, C4a and C5a work as potent inflammatory cytokines causing smooth muscle contraction, vascular permeability and degranulation of mast cells and basophils. 
• These proteins are known as anaphylatoxins due to their ability to induce anaphylactic symptoms independent of immunoglobulin E. 
  

B-Cells 

• Involved in humeral response.
  
• The immune cells involved in production of immunoglobulin (Ig) or antibodies & protect against extra-cellular pathogens.
  
• B-cells display a highly specific B-Cell receptor (BCR) with affinity for one antigen only.
  
• This receptor is the membrane bound form of the Ig molecule that would be secreted by the B-cell when activated.
  
• When the BCR interacts with its antigen, it internalises the receptor-antigen complex, processes the antigen and then displays antigenic peptides in association with MHC class II at its cell surface.
  
• The B-cell then acts as an APC to helper T- cells that have been activated by the same pathogen.
  
• The T-cells then release the cytokines IL-2, IL-4, IL-10 and IL-13 which induce B-cell activation.
  
• Following activation, B-cells proliferate and differentiate into a large number of identical plasma and memory cells in a process known as clonal expansion.
  
• Plasma cells are responsible for the secretion of immunoglobulin whereas memory cells enter a resting state and are involved in producing a rapid, vigorous response to subsequent infection with that particular pathogen. 
  

T-Cells

- Have a role in the defence against both intra-cellular pathogens (such as viruses) and extra-cellular pathogens (such as bacteria).

Immunoglobulin

• A protein complex that consists of 2 identical heavy chains and 2 identical light chains.
  
• At the amino-end there is a binding site that is highly specific for its antigen.
  
• This region is called the variable region as this is where the diversity in the heavy and light chains leads to specificity to different antigens.
  
• The carboxy- terminal of the peptide is known as the constant region and is responsible for interaction with antibody receptors on neutrophils, macrophages and mast cells, further it is able to induce activation of the complement cascade.
  
• Immunoglobulin molecules can be classified into five isoforms depending on the type of the heavy chain (see link at bottom)
  
• Diverse role in the defence against both intracellular and extracellular infection.
  
• IgE activates mast cells. It is produced by activated B-cells. Although it is the least abundant immunoglobulin, it is vital for combatting parasitic infection.
  

• Anatomical barriers - 1st line defence, most significant barrier being the skin.
  
• Increased incidence of both local and systemic infections when this barrier is compromised (burns/skin complaints). 
  
• Respiratory, gastrointestinal and genito-urinary tracts have specialised mucous membranes.
• IgA, an antibody, secreted by mucosal cells that binds to pathogens and their toxins to neutralise and deactivate them
• Cells and proteins of the innate immune system provide a line of defence that is present from birth.
• Response is not altered by subsequent invasion & cells etc have no ’memory’.
• At tissue level, the innate immune system provides non-specific defences that prevent microbial growth & info
• This system responds to invasion through cellular and complement protein responses.
• The cellular response is bought about by leucocytes, which can be
  granulocytes (neutrophils, eosinophils and basophils) or agranulocytes (monocytes and lymphocytes).
• The innate system aims to destroy the invading pathogens rapidly to prevent spread of infection -(eg. phagocytosis)
• Macrophages and neutrophils = primary phagocytic cells of the innate system
• Macrophages are the primary phagocytic cells and are one of two cell lines of cells that mature from monocytes.
• Monocytes differentiate into dendritic cells. These have limited phagocytic activity but do play a crucial role in linking the innate system with the acquired immune response through their role as antigen presenting cells.
• In order for phagocytosis to take place, the pathogen must first be recognised as being ‘foreign’. Via interactions between specialised cell-surface receptors on the macrophage with ‘pathogen associated molecular patterns’ (PAMPs) which are expressed by microbes.
• An example of this interaction is the toll-like receptor (TLR) expressed by macrophages recognising lipopolysaccharide (LPS) on gram negative bacteria.
• Not all invaders are extracellular. Viruses infect host cells and can evade phagocytosis by macrophages. 
• Innate immune system is able to combat intracellular infections through another cell line - the natural killer (NK) cell. 
• Through the pro-inflammatory cytokines, these cells are recruited to the site of infection and identify infected cells through the display of altered or absent major histocompatibility (MHC) class 1 complexes
  

Dr. David Lyness

www.propofology.com