3 - Innate immunity Flashcards
What is innate immunity?
- Present from birth
- Distinguishes from self and non self using pattern recognition receptors (PRRs)
- Does NOT use highly diverse antigen-specific receptors (as used by lymphocytes)
- Recognises damage to self
- Not enhanced upon second exposure (no memory)
- Uses cells and soluble components in body fluids
- Provides a rapid response (minutes to hours) that cooperates with and helps to direct subsequent antigen-specific, adaptive immunity.
What do PRRs recognise?
Pathogen associated molecular patterns (PAMPs)
e.g. lipopolysaccharide, flagellin
What do phagocytic cells do?
Engulf invading organisms, try to kill them, release signals to alert other cells to the infection.
Name 4 phagocytic cells
Neutrophils
Monocytes
Macrophages
Dendritic cells
What do neutrophils do?
- Polymorphonuclear leukocytes
- Abundant, relatively short-lived.
- Circulate in blood and migrate out into tissues to sites of damage/infection.
- Highly phagocytic cells, antigen uptake is more efficient after opsonisation, Antibody and complement function as opsonins in this way.
- Neutrophils have multiple killing mechanisms, the most important of which involve the oxygendependent respiratory burst.
What is opsonisation?
The process of coating of micro-organisms with proteins that are able to be bound by phagocytes.
What is neutrophil deficiency associated with?
Infections due to extracellular bacteria ans fungi.
What are macrophages?
The other main phagocytic cells, found in tissues
What are monocytes?
- The blood form of macrophages.
As well as engulfing and trying to kill invading organisms, macrophages are particularly important for their role in secreting “alarm” cytokines, in particular interleukin-1 (IL-1), IL-6, IL-8 and tumour necrosis factor alpha (TNF-α).
What are dendritic cells?
- Found in the skin and near mucosal epithelia
- They recognise pathogens, secrete cytokines, engulf pathogens and migrate to local lymph nodes to present antigens to the adaptive immune system.
What are cytokines?
- A large family of many different small secreted proteins involved in cell to cell communication.
- They have biological effects at very low concentrations, are short-lived, and generally act locally.
- They often have effects on more than one cell type, and are produced in combinations rather than individually in isolation, leading to a “cytokine milieu”or “cocktail”.
How do cytokines function?
They function by binding to specific receptors on the surface of cells.
What are the 5 different categories of cytokines?
Interleukins – communicate between leukocytes
Interferons – have anti-viral effects
Chemokines – required for chemotaxis and recruitment of cells to particular sites
Growth factors – required for development of cells of the immune system
Cytotoxic – can induce cell death e.g. tumour necrosis factor
What is compliment?
A complex series of proteins in serum and in tissues which form a triggered enzyme cascade system, leading to:
- opsonisation of micro-organisms
- direct killing of microorganisms
- promotion of inflammation
- recruitment of leukocytes
Which cells may be activated my compliment?(anaphylatoxins)
What does this cause them to do?
Mast cells
- They degranulate
- Leading to vasodilation
- Increased vascular permeability
What are the 3 compliment pathways?
Classic pathway - Antigen/antibody
Lectin pathway - MBL= mannanbinding lectin, CRP = C-reactive protein
Alternative pathway - Bacteria
What does local acute inflammatory response involve?
Involves... macrophage activation, cytokine secretion, endothelium activation, leukocyte extravasation and chemotaxis, neutrophil phagocytosis and killing.
What increases vascular permeability?
- Compliment activation
- Opsonisation
- Mast cell degranulation
- Kinin cascade activation
What is an acute phase systemic response?
- Occurs 1-2 days after local acute inflammatory response.
- Fever
- Increased production of leukocytes
- Production of acute phase proteins by the liver; this is a cytokine induced reaction (IL-1, IL-6 and TNFα). They help fight the infection.
Name examples of acute phase proteins
C-reactive protein Mannas-Binding lectin Serum amyloid A Compliment components Fibrinogen (for clotting)
What are natural killer cells?
- Large granular lymphocytes (5-10% of peripheral blood lymphocytes) with cytotoxic activity.
- Important in defence against tumours and viral infections (Herpes viruses in particular).
- No antigen-specific receptor, but express complex sets of both activating and inhibitory cell surface receptors: whether to kill or not is a balance of different signals.
Activated NK cells also secrete the cytokine interferon-γ.
Brief summary of cells and humeral innate immunity.
CELLS:
phagocytes (bacteria), Natural killer cells (viruses)
HUMORAL:
compliment (bacteria), interferons (viruses)
What are interferons?
A protein which inhibits a virus replicating.
