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Infection and Immunity Lecture Notes
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2nd Year BSc Biomedical Science Notes
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BI505 Infection and ImmunityInfection and Immunity
Innate Immunity
Innate Immunity: Complement
The Adaptive Immune Response
Viruses and the Immune Response to Viral Infection
The Antibody Molecule
Ab Gene Rearrangement and B-cell Activation
Antigen Processing and Presentation to T-cells
Cell-Cell Communication
Immunopathology
Epidemiology of Infectious Diseases
Introduction to Viruses
Parasitic Infections
Mycology: Fungal Infections
Medically Important Bacteria
Medically Important Bacteria II
The CNS and Eye Infections
Gastrointestinal Tract Infection
Bacterial Gastrointestinal Tract Infection
Bacterial Urinary Tract Infection
,Infection and Immunity
PAMPs
- Pathogen-associated molecular patterns.
- These are antigens on the pathogen cell surface that trigger an innate immune
response.
- These can be bacterial endotoxins, such as lipoteichoic acids of gram-positive
bacteria, or lipopolysaccharides of gram negative bacteria; flagellin of flagella;
unmethylated CpG dinucleotides of bacterial DNA and combinations of sugars.
- PAMPs are recognised by pattern recognition receptors (PRRs), such as toll-like
receptors.
DAMPs
- Damage-associated molecular patterns.
- These are components that are usually found within cells but get released when
our cells are damaged.
o ATP, interleukin 1α, uric acid, calcium-binding cytoplasmic proteins and
DNA-binding nuclear proteins.
Differences between MHC proteins and TLRs
- MHC proteins are cell surface proteins that display peptide fragments of
proteins that were broken down inside the cell.
- The immune system is constantly checking for non-self antigens and so MHC
proteins act as the HR department for the cell.
- If invading pathogens enter the cell, their exogenous proteins are degraded and
sent to the cell surface to be displayed on the MHC.
- MHC proteins help stimulate the adaptive immune system, whereas TLRs
employ the innate immune system by recognising PAMPs or DAMPs.
PRRs
- Pattern recognition receptors are endogenous receptors that recognise non-
self antigens. TLRs are one type of PRR.
Cytotoxic T cells
- T lymphocytes that have lytic capabilities and are important in destroying
altered self cells (infected or tumour cells).
- CTLs contain cytoplasmic granules that store perforin and granzymes. Perforin
is secreted when the CTL docks to infected cells and insert themselves into the
cell surface membrane. They operate in the same way as complement proteins
to lyse the cell.
- Perforin pores also enable the uptake of granzymes into the cell, which trigger
apoptosis by DNA fragmentation.
Action of CTLs
- 1) Conjugate formation
o TLR-CD3 of CTL recognises antigen by MHC I. Then integrin receptor
LFA-I binds to ICAMs on the cell surface → conjugate.
- 2) Membrane attack by perforin, granzymes or Fas.
- 3) Dissociation.
- 4) Apoptosis of target cell.
, - 5) CTL recycling.
Fas-mediated killing
- CTLs that don’t have granzymes or perforin mediate cytotoxicity through Fas
protein. Fas is a transmembrane protein on normal cells but when crosslinked
with its ligand on CTLs, then it will activate apoptotic signalling cascades
involving caspases.
- Fas forms a Fas:FasL complex with its ligand.
Innate Immunity
- Intestinal crypts contain Paneth cells, which are specialised to produce several
kinds of antimicrobial proteins: α-defensins and RegIII (an antimicrobial lectin).
o Paneth cells are found at the bottom of the intestinal crypts.
o Paneth cells as well as phagocytes secrete lysozyme.
α-defensins
- Amphipathic peptides that disrupt the cell membranes of microbes. They do this
by inserting themselves into the microbial membrane (i.e. complement protein
action).
- Cryptdins are constitutively secreted by Paneth cells.
RegIII γ
- A Ca2+-dependent, carbohydrate-binding secreted or transmembrane protein.
- A C-type lectin that binds to peptidoglycans on bacterial cell walls.
- Preferentially kills gram positive bacteria.
- Lysozyme also digests the cell walls of gram positive and negative bacteria.
o They cleave beta-1,4-linkages.
o More effective on gram positive as they do not have an LPS layer
shielding their peptidoglycan layer.
- Antibiotics kill many of our commensal bacteria and can confer a vulnerability
to pathogenic bacteria, which secrete toxins that can cause necrosis of mucosal
tissue.
o This is because commensal bacteria outcompete the pathogenic
bacteria, providing an aspect of defence in the gut.
o Necrosis of mucosal barrier can confer food allergens as undigested
particles may get into the blood.
- Primary lymphoid organs are those that produce white blood cells or help in
their development.
Responses to a new infection
- Innate = infection + recognition + removal.
- Early induced innate = Infection + recognition + inflammation + removal.
- Adaptive = infection + antigen presentation + recognition + clonal expansion +
removal.
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