Innate immune response Flashcards
What are the innate physical barriers to infection?
Skin Mucus Gastric acid Bile salts Normal microbiota (throat, colon, vagina)
What is the overall effect of IIS?
Production of a state of inflammation in the infected tissue → pain, heat, redness and swelling
What happens when the physical barrier to infection has been breached?
Phagocytes are the second line of defence
Examples of phagocytes
Tissue macrophages
Neutrophils (migrate to damaged tissue)
DCs → carry away microbic material to lymphoid tissues
Monocytes → recruited to the inflamed tissue to take the place of DCs
What are the classes of PRR? What do they recognise?
- TLRs (extracellular)
- TLR2 → peptidoglycan
- TLR4 → LPS
- TLR9 → bacterial DNA - C-type lectin receptors (extracellular)
- mannan-binding lectin
- dectin-1 - NLRs (intracellular)
- peptidoglycan
What are the cells of the innate immune system?
APCs (macrophages and monocytes, DCs)
Granulocytes (neutrophils, eosinophils, basophils and mast cells)
Innate lymphatic cells (NK cells)
What type of cells are macrophages (origin)?
myeloid
What are the two distinct origins of macrophages?
Embryonic yolk sac derived tissue macrophages (long-lived, self-renewing)
Bone marrow-derived infiltrating monocytes)
What are the two major classes of macrophage?
- tissue resident (e.g. Kupffer cells, microglia) → mediate homeostasis, repair and remodelling
- infiltrating monocytes → become inflammatory macrophages mediatign antimicrobial functions
What can macrophages be activated by?
Activation alternatively by Endotoxin, IFN-gamma, IL-4, IL-13. Pro-inflammatory Cytokines (TNF-a, IL-1, IL-6). Other Cytokines (IL-10, IL-12).
What two types of behaviour may macrophages display when encountering pathogens?
- phagocytosis
2. secretion of molecules that are either antimicrobial effector molecules or immune regulatory messenger molecules
By which pathways may phagocytosis occur?
Opsonisation-dependent or opsonisation-indepent pathways
What opsonin receptors do macrophages have?
C1qR, CR3 or Fc receptors
Which PRRs are specific to macrophages? What do they do?
Scavenger receptors → mediate uptake of modified LDL by macrophages to give foam cells
Describe the mechanism of phagocytosis - what are the mechanisms by which killing can occur?
- phagolysosome through cytoskeletal rearrangement
Killing can occur via the following mechanisms:
1. oxygen-dependent → oxidising radicals and oxidised halides → respiratory burst
2. oxygen-independent antibacterial mechanisms → enzymatic and non-enzymatic mechanisms → proteases, phospholipase, etc
3. reactive nitrogen species → NO regenerated by the phagocytes enzyme iNOS
What cytokines and GF may macrophages release and what do these do?
IL-1
IL-6
TNF-alpha
Macrophages also produce IL-8 which is a chemokine and attract neutrophils and T cells to the site of infection
Aside for phagocytosis and production of cytokines, what else do macrophages do?
Professional APC - MHCII → ANTIGEN PRESENTATION
What cells are the main inducers of the adaptive immune response?
DCs
Where are DCs mainly located?
kin and mucosa of gastrointestinal, respiratory and genitourinary tracts although some are also derived from monocytes
Main function of DCs
Engulf and present antigens via MHCI to cytotoxic cells and MHCII to Th cells
Ability to collect antigens and then migrate from these barrier locations, through draining lymphatic vessels, into lymph nodes
When in lymph nodes, they prime naive T cells to be activated
What do neutrophils do?
- phagocytosis of opsonised microbes (they are NOT APCs)
- NETs → dying neutrophils extrude nuclear material, DNA and histones, making a net to which antimicrobial proteins are tightly bound → allows them to kill pathogens extracellularly
What types of disease is eosinophil concentration raised?
Parasite infection
Hypersensitivity diseases
Functions of eosinophils
- thought that parasites become coated by IgE and eosinophils possess IgE receptor, this allows them to attach and release eosinophilic granules to damage larvae
- also have leukotrienes and peroxidases
- another function may be to REDUCE inflammation → granules contain histaminase
What are eosinophils stimulated by?
IL-5 and eotaxin
