Present in babies, and protective

The ER “medical technician”

Macrophages –

Very important, particularly in this early immune response

Phagocytosis – recognise and remove unwanted particles

Secrete lysozymes to break down and kill particles

Secrete interferon to activate anti viral mechanisms

Secrete molecules to activate , eg cytokines

Complement

The complement system is a group of more than 20 tightly regulated, linked proteins that act to promote inflammation and eliminate invading pathogens. Complement proteins are produced by the liver, and are present in the circulation as inactive molecules. When triggered, they enzymatically activate other proteins in a rapidly amplified biological cascade analogous to the coagulation cascade.

There are three mechanisms by which the complement cascade may be triggered.

• The alternative pathway is directly triggered by binding of C3 to bacterial cell wall components such as lipopolysaccharide of gram negative bacteria and teichoic acid of gram positive bacteria.
  
• The classical pathway is initiated when IgM or IgG antibody binds to antigen, forming immune complexes. This induces a conformational change in the antibody, exposing a binding site for the first protein in the classical pathway, C1. Changes in C1 after binding result in activation of the cascade.
  
• The lectin pathway is activated by the direct binding of mannose binding lectin to microbial cell surface carbohydrates. This mimics the binding of C1 to immune complexes, and directly stimulates the classical pathway, bypassing the need for immune complex formation.

Activation of complement by any of these pathways will result in the activation of C3, the major amplification step in the complement cascade. C3 activation is followed by the final common pathway, where the complement proteins C5-C9 assemble together to form the membrane attack complex. This can insert into and puncture target cell walls, leading to osmotic cell lysis. This step is particularly important in the defence against encapsulated bacteria such as Neiserria and Haemophilus influenza.

The complement fragments generated by activation of the cascades can also act as opsonins, rendering microorganisms more susceptible to phagocytosis by macrophages and neutrophils . In addition, they are chemotactic agents, promoting leukocyte trafficking to sites of inflammation. Some fragments act as anaphylotoxins, binding to complement receptors on mast cells and triggering release of histamine, which increases vascular permeability.

The products of complement activation also help to target immune complexes to antigen presenting cells, providing a further link between the innate and the acquired immune systems. Finally, activated complement products dissolve the immune complexes that triggered the cascade, minimising bystander damage to surrounding tissues.

Category: Pathology Notes