Innate Immunity Flashcards
Adaptive Immune response consists of
the production of…
antibodies and specific
subsets of T cells
What do invertebrates have only?
innate
Recall some components of innate immunity(5)
• Phagocytes- Macrophages/Dendritic cells/granulocytes/neutrophils • Inflammation • Cytokines/chemokines • Complement 6. Natural Killer cells
What is inflammatory response?
• A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components
What does inflammatory response enhance?(4)
- Enhanced permeability and extravasation
- Neutrophil recruitment
- Enhanced cell adhesion
- Enhance clotting
What triggers inflammation?
• Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection
What are cytokines?(2)
- Act to modify the behaviour of cells in the immune response
- Most of these are called interleukins (eg. IL-1)
What are interleukins?
Names for cytokines
What are chemokines?
• Act as chemotactic factors – i.e. they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection
Name some receptors found on macrophages
mannose receptor
- complement receptor
- scavenger receptor
- dectin- b glucan receptor
What are PAMPs?(3)
• Molecules present only on pathogens and not on host cells
- • Essential for survival of pathogens
- • Invariant structures shared by entire class of pathogens
What are the structures found on gram negative cell surface?
lipopolysaccharides (LPSs) found in outer membrane
What are the structures found on gram positive cell surface?(3)
teichoic acid,
lipoteichoic acid,
3. peptidoglycan found in outer membrane(cell wall)
Name so other PAMPs?
- Bacterial flagellin
- Abnormal protein glycosylation
- Abnormal nucleic acids – viruses
What are PRRs?
- Host factors that specifically recognise a particular type of PAMP
- They are germ-line encoded
Recall the three classes of PRRs
o Extracellular – they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen
o Intracellular (cytoplasmic) – they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen
o Secreted – they act to tag circulating pathogens for elimination
What are interferons?
- Interferon(cytokines) binds to receptors on other cells which triggers the production of about 400 enzymes
- The enzymes create a hostile environment for any virus that is trying to replicate.
What is the complement system?(2)
• A system of secreted proteins made in the liver that recognise PAMPs on the surface of microbes and “decorate” or “tag” them.
- The microbes are then cleared by phagocytosis, “opsonised” or they have holes punched in them.
Where are interferons secreted from?
the liver
What are the three ways of activating the complement system
- (i). Recognition of LPS and other PAMPs by the C1q component of “classical” pathway
- (ii). Non-host glycosylation is recognised by MBP(mannose binding protein/lectin) and other lectins to activate the “lectin” pathway
- (iii). Membranes that are recognised as “non-self” activate the “alternative” pathway
Complement activation involves a proteolytic cascade
What do natural killer cells do?
• NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells.
- • Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces, AND up-regulation of activating ligands
What percentage of WBCs as NKs
• 4% white blood cells
Describe the structure of NKs
• Lymphocyte-like but larger with granular cytoplasm
What causes target cell destruction?
caused by cytotoxic molecules called granzymes & perforins
What are some diseases that can be caused by defects in the complement system?(2)
- core defects(C3) causes autoimmune diseases such as lupus
2. non-core defects linked to susceptibility to specific types of pathogens such as Neisseria
What disease can arise from macrophage deficiency?
Chronic granulomatous disease (CGD); No oxidative burst for bacterial killing
- IRF8 mutations linked to susceptibility to TB
What is a syndrome that can arise from constitutive production of inflammatory cytokines?
• Aicardi–Goutières syndrome
• Lack of interferon-responsiveness causes…
sensitivity to viral infection (e.g. measles)
Compare innate and adaptive response
Innate: macrophages, neutrophils, Dcs 2. fast 3. no memory required 4. receptors are pattern recognition 5. PAMPs
Adaptive: lymphocytes 2. slow 3. memory cells 4. receptors are Immunoglobins and TCR 5. billions of possible antigens
what is IL-1?
→Main producer = Macrophages + keratinocytes
→Acts upon = lymphocytes + liver
→Effect = Enhances response
→ Induces acute-phase protein secretion
what is IL-6?
→ Main producer = Macrophages + dendritic cells
→ Acts upon = lymphocytes + liver
→ Effect = Enhances response
→ Induces acute-phase protein secretion
what is CXCL8 (IL-8)?
→Main producer: Macrophages + dendritic cells
→Acts upon: Phagocytes
→Effect: Chemoattractant for neutrophils
what is IL-12?
Main producer: Macrophages + dendritic cells
→ Acts upon: Naive T cells
→Effect: Diverts immune response to type 1, →proinflammatory, cytokine secretion
what is TNF - alpha?
Main producer: Macrophages + dendritic cells
→Acts upon: Vascular endothelium
→Effect: Induces changes in vascular endothelium (expression of cell-adhesion molecules (E- + P- selectin), changes in cell-cell junctions w/increased fluid loss
how do macrophages “see” microbes?
→Passive sampling
→ Scavenger receptors
→Engulfing apoptotic cells
Lectin receptors
→Ligand: terminal mannose and fucose
→Outcome: phagocytosis
Scavenger receptors
→Ligand: bacterial cell walls modified low-density lipoproteins
→Outcome: phagocytosis
Toll-like receptors (TLRs) (surface and endosomal)
→Ligand: LPS (together with CD14) lipoproteins unmethylated CpG flagellin ds RNA; ss RNA (in endosomes)
→Outcome: inflammation: cytokine release (TNF, IL-1, IL-12) enhanced killing: reactive oxygen species, NO)
NOD-like receptors (NLRs) (cytoplasm)
→Ligand: peptidoglycan from Gram positive and negative bacteria some viral DNA and RNA (indirect?)
→Outcome: inflammation: cytokine release (IL-1, IL-8)
RIG-like receptors (RIG-1 and MDA5) (cytoplasmic)
→Ligand: dsRNA and 5’-triphospho RNA
→Outcome: type I interferon production
how does cell death happen?
→Perforin + cytotoxic granules
→Engagement of death receptors
NK cells bind
cells bind HLA-E which carries in its groove a peptide from the leader sequence of classical class I MHC molecules
CMV (Cytomegaloviruses ) has four gene products which
→reduce the expression of Class 1 MHC molecules and two class I MHC homologues (UL18 & M144), that give a negative signal to NK cells
