Innate Immunity

what are some key components of the innate immune system

• epithelial barriers

• phagocytes

  • neutrophils, monocytes, macrophages, dendritic cells

• type II immunity

  • mast cells, eosinophils, basophils

• lymphoid cells

  • ILC1-3 & NK cells

• innate T cells

  • NKT cells, MAIT cells, γδ T cells

• complement

what are some components of the adaptive immune system

• T cells

• B cells

  • antibodies

how do the innate & adaptive system respond

innate - response is rapid, can be detected within quickly

adaptive - response is slower, detected after several days

why is the innate immune system so good a detection

innate immune cells detect the expression of many different types of pattern recognition receptors (PRR)

• these recognize structures of microbes not expressed in mammals

what are pattern associated molecular patterns (PAMPS)

structures that are present on microbes but not present in mammals

• these are recognised by immune cells

why is the adaptive immune system so selective

each lymphocyte displays an antigen receptor with a unique single specificity

what is important to note about PRR (regarding germline)

they are germline encoded & broadly specific

• cannot distinguish PAMPS from different species

• EXAMPLE: can recognize LPS cant distinguish e. coli vs salmonella

what is somatic recombination

the process by which DNA segments are rearranged (V, D, J cut & rejoined) to create new combination

• gives rise to receptor diversity

summary of innate & adaptive immunity

how are epithelial cells involved in an immune response

they secrete chemokines & cytokines at the basal surface that recruit immune cells

describe mucociliary transport

refers to the movement of mucus (produced by goblet cells)

• usually to remove microbes from the body (e.g. lungs)

what is meant by complement

a series of serum proteins (C1-C9) that collectively form a biochemical pathway, has 3 immunological outcomes:

• inflammation

• opsonisation

• microbial lysis

what are the 3 ways of activating complement

1. the alternative pathway - an ancient non-specific chemical reaction

2. the classical pathway - activated by complexes of antibody with antigen

3. The lectin pathway - triggered by recognition of unique microbial carbohydrates

what is important to note about all 3 pathways

all pathways create a C3 convertase, after which the pathways converge

describe the mechanism of the alternative pathway

C3 spontaneously hydrolyses to from C3a & C3b

• C3b then forms a C3 convertase

• triggers rest of pathway

this is non-specific with no specific recognition event

what is the mannose binding lectin

a soluble pattern recognition receptor found in serum that binds to mannose found in the surface of microbes

describe the mechanisms of the lectin pathway

proteases associated with MBL then cleave C4

• rest of pathway is identical to classical pathway

describe the mechanism of the classical pathway

1. C1q recognises IgG or IgM bound to antigen

2. C1q also contains proteases that cleave C4

3. C2 is cleaved generating the C3 convertase

4. C3b converts the C3 convertase into a C5 convertase

describe late stages of complement activation (all pathways)

1. C5 gets cleaved into C5a & C5b

   • C5a is a potent pro-inflammatory factor

2. C5b is stuck on the cell/microbe surface and initiates the assembly of the MAC (C5b, C6, C7, C8, C9)

3. MAC generates pores in membrane leading to cell lysis by osmotic shock

how do complements drive inflammation & leucocyte recruitment

the proteolysis of C3 & C5a release the soluble fragments C3a & C5a

• leucocytes have receptors for C3a & C5a

C3a & C5a are chemo-attractants (attract leucocytes to the site of infection)

how do complements drive opsonization & phagocytosis

all complement pathways deposit C3b on the pathogen surface

• phagocytes have receptors for C3b

A microbe covered in C3b is then recognized by the complement receptor which activates the phagocyte leading to phagocytosis

what is some general information on macrophages

• antigen presenting cell

• can differentiate into several different forms

  • inflammatory macrophages

  • anti-inflammatory macrophages

what is the function of monocytes

an emergency source of macrophages

• upon infection, monocytes leave the circulation & differentiate into macrophages

• arrive slower than neutrophils

what is some information about neutrophils

• rapidly migrate out of circulation to site of infection

• can’t present antigen, limited cytokine secretion

• effective killers of organisms growing extracellular

what are the 3 mechanisms by which neutrophils can kill

1. phagocytosis

2. degranulation: release granules that contain anti-bacterial proteins

3. neutrophils extracellular traps (NETs), release a DNA web that traps & destroys bacteria

describe the process of phagocytosis

1. PRR specialised in uptake bind to microbes

2. involution of the phagocyte membrane leads to microbial uptake into the phagosome

3. The phagosome fuses with the lysosome – an acidic vesicle rich in degradative enzymes

4. In the phagolysosome two enzymes play an important role in killing the microbes:

   • Phagocyte oxidase - Reactive Oxygen Species (ROS)

   • Inducible Nitric Oxide synthase - Nitric Oxide