Peschel

• our bodies carry ten times as many bacterial cells as human cells

• Most microbes in the gut

• The consortium of colonizing microbes as ben dubbed the human microbiota or microbiome

• Microbe populations change constantly

Bacteria normally found at various nonsterile body sites that are not causing problems

• densest microbiome

• Contains 10^9-10^11 bacteria/g of feces, ration of 1000 anaerobes :1 facultative organism

• Organisms that inhabit the intestine include:

  • Bacteriodetes e.g. Bacteroides vulgatus (anaerobe)

  • Enterobacteriacea e.g. Escherichia coli (facultative anaerobe)

  • Firmicutes e.g. Clostridium species (anaerobe)

• layers of dead keratinocysts protect deeper tissue

• Dryness, high salt, antimicrobial fatty acids prevent bacterial growth

Tight junctions prevent entry of microbe, mucus prodution interferes with bacterial adherence

“Ciliar escalator” removes particles & microbes along with mucus

Low pH (2-4) sterilizes ingested food

• reacts very fast

• Based on phagocysts & antimicrobial molecules

• Recognition through inherited receptors detecting microbial components (few dozen receptors)

• “Microbe-associated molecular patterns” (MAMPs) are recognized by “pattern recognition receptors” (PRRs)

• needs days/ weeks

• Based on antibodies & lymphocytes

• Recognition through receptors generated by recombination (few million)

• circulate in blood stream

• Enter infected tissue following inflammatory signals

• circulate in blood stream

• Produce pro-inflammatory cytokines

• Can enter tissue & develop into macrphages or dendritic cells

• reside as sentinels in sterile tissue

• Detect & eliminate invading microbes

• Alert & recruit neutrophiles

• Present antigens & initiare adaptive immunity

• phagocytes must avoid attacking host cells -> foreign particles must be labeled

• Innate immunity: opsonization by complement factor C3b

• Antimicrobial peptides (defensines,..): damage bacterial membranes

• Antimicrobial enzymes (lysozyme: can cleave sugar bonds of peptidoglycan, lipases,..)

• “Oxydative burst” (NADPHoxidase, myleoperoxidase): toxic oxygen & nitrogen compounds

• Terminal complement components: “membrane attack complex”

1. Recruitment of leukocytes (C3a, C5a)

2. Elimination by opsonic pahgocytosis (complement receptors)

3. Killing of microorganisme by “membrans attack complex” (gram- bacteria)

1. Antigen-antibody complexes

2. Binding of mannan-binding lectin (MBL) to microbial sugars

3. Direct linking of C3b

• relies on circulation lymphocytes called memory B & T cells

• From birth the immune system is able to adapt & recognize billion of possible foreign antigens

• From during an infection to remembering ir for years

• recognition via antibodies

• Presentation of soluble antigens in MHC I & II

• Production of antibodies after activation

• detection via T-cell receptors

• Helper T cell: activation of macrophages & B cells

• Cytotoxic T cell: killing of infected human cells

• phagocytosis & inactibvation of microorganisms

• Release of cytokines & inflammation mediators

• Presentation of antigens in MHC I & II

• phagocytosis of microbial molecules

• Release of cytokines & inflammation mediators

• Presentation of antigens in MHC I & II

• an antibody (=immunoglobulin) is a Y- shaped structure made up of four polypeptides

• Two large heavy chains & two smaller light chains connected by disulfide bonds

• the immune syste does not recognize the whole microbe but innumerbale tiny pieces of it

• Each segment of an atigen that elicits an immune response is calles an epitope or an antigenic determinant

Highly complex process

1. antigen presenting cells (APCs) ingest microbes, digest macromolecules & present antigens in MHC II molecues

2. APCs migrate to lymph nodes activate antigen specific CD4 T cell

3. Antigen specific T & B cell encounter inudces antibody production

4. Specific antibodies promote microbe phagocytosis & elimination

5. Some specific T & B cells develop into memory cells

-> takes few weeks

1. Antigen presenting cells (APCs) present antigens of intracellular pathogens in MHC I molecules

2. APCs migrate to lymph nodes; activate antigen specific T cells

3. T cell differentiates into cytotoxic CD8 T cell

4. Kills infected host cells presenting antigen in MHC I molecules

5. Some specific T cells develop into memory cells

T cell receptor recognizes MHC antigen complex

Antigen presenting cells use MHC I & I molecules

As a safety measure T-cell activation requires a second signal by microbial MAMPs

IgM forms pentamers, IgA dimers

IgM is the first Ig produced; particular aglutination capacity

IgA dimers are translocated to epithelial surfaces

Antibody diversity results from somatic recombination of gene fragmenst -> 10^11 different antibody molecules in humans