LECTURE 4 (Innate immune system) Flashcards
What is the function of the Innate Immune System?
It is responsible for reacting quickly to invading microbes and for keeping the host alive while the adaptive immune system is developing a very specific response
Are innate immune defences present at birth? (YES/NO)
YES
What are the characteristics of the Innate Immune System?
- Very limited diversity for antigen (Primitive and broad)
- Attack all microbes the same way no matter how many times they have seen the same pathogen (Unspecific)
- Immediate
- Fast
- No memory
What are the two ways that the innate immune system handles pathogens?
- Inflammation -> Elimination of microbes
- Interferons & Natural killer cells -> Elimination of viruses
What are the different Cytokines?
- Chemokines
- Interleukins
- Tumour Necrosis Factor
- Interferons
What happens when physical barriers are breached?
Microbes may gain access to the tissues where they come in contact with PHAGOCYTIC CELLS (neutrophils, macrophages and dendritic cells) which produce CYTOKINES (chemical messengers) -> Initiates an INFLAMMATORY RESPONSE
What can happen once pathogens gain access to the blood?
The adaptive immune system may have to take over to resolve the infection and eliminate the pathogen
What are considered “early defence against pathogens”
- Physical (anatomic) barriers
- Physiologic barriers
- Innate cellular response
- Inflammation
What are the main portals of entry for most pathogens?
- Skin
- Respiratory tract
- GI tract
What are the properties of the surfaces that pathogens can enter into?
- Lined with epithelial cells that can produce DEFENSINS and INTERFERONS (antimicrobial products)
- Contain specialised intra-epithelial lymphocytes (IEL) called γδ T cells
[considered part of innate immunity as they only recognise shared microbial structures]
How do Tears aid Innate immunity?
- Wash away irritating substances and microbes
- Lysozyme kills many bacteria
How does skin aid Innate immunity?
- Provides a physical barrier to the entrance of microbes
- Acidic pH discourages growth of organisms
- Sweat, oil and fatty acid secretions kill many bacteria
How does the Respiratory tract aid Innate immunity?
- Mucus traps organisms
- Cilia sweep away trapped organisms
How does the GI tract aid Innate immunity?
- Large intestine has normal bacterial inhabitants that keep invaders in check
- Stomach acid kills organisms
- Saliva washes microbes from teeth and mucous membranes of mouth
How does the Bladder aid Innate immunity?
Urine washes microbes from urethra
What are the different Physiological barriers?
- Temperature
[when inflammatory response is initiated in the local tissues -> cytokines acts systemically to alter temp set point in hypothalamus resulting in fever] - pH
What are the different Chemical barriers?
- Lysozyme (present in tears, saliva, breast milk and mucous) can break down the CELL WALL PEPTIDOGLYCAN of bacteria
- DEFENSINS found within phagocytes can form PORES in bacteria and fungi
- IFN-α and IFN-β are ANTI-VIRAL INTERFERONS -> direct anti-viral effect by inhibiting NASCENT PROTEIN SYNTHESIS in cells
How do Phagocytic cells recognise pathogens?
via shared molecules that are not expressed on host cells
- PATHOGEN-ASSOCIATED MOLECULAR PATTERNS (PAMPs) = molecules shared by pathogens of the same type
- DAMAGE-ASSOCIATED MOLECULAR PATTERNS (DAMPs) = released from dying or damaged cells
What are Pattern Recognition Receptors (PRRs)?
Receptors of the innate immune system
What are the properties of Pattern Recognition Receptors (PRRs)?
- Present intrinsically
- Encoded in the germline genes
- Not generated through somatic recombination in the same way lymphocyte receptors are generated
What is the Inflammasome?
- Expressed in myeloid cells as a SIGNALLING SYSTEM for detection of pathogens and stressors
- Activation results in production of IL-1b and IL-18 (potent inflammatory cytokines)
What does a mutation in signalling molecules effecting TLRs lead to?
Recurrent, severe bacterial infections (pneumonia)
What do Gain of function mutations in inflammasome lead to?
- Gout
- Atherosclerosis
- Type II diabetes
What do NOD-2 mutations result in?
IBD (Inflammatory Bowel Disease)
What do IL-12 and IFN-γ receptor deficiencies result in?
Recurrent infections with intracellular bacteria (Mycobacterium)
