Immunity (innate) lecture 1

Core Functions of Innate immune system

• Defence

• Handles a wide diversity of threats, explaining its complexity

• Provides immune surveillance against tumours (partial protection)

• Forms the basis for vaccination strategies

• Can be pathogenic l when dysregulated

Chronic or excessive immune responses can cause what diseases?

• Sepsis

• Autoimmune diseases

• Type 2 Diabetes

• Chronic inflammation

Differences between innate vs Adaptive immunity?

Innate Immunity

• Non-specific

• Immediate response

• No immunological memory

• Present from birth

Adaptive immunity

• Antigen-specific

• Delayed onset

• Immunological memory

• Improves with repeated exposure

components of innate ?

• Humoral

  • Pattern recognition receptors (PRRs)

  • Complement proteins

  • Enzymes

  • Cytokines

• Cellular

  • Phagocytes (macrophages, neutrophils)

  • Natural Killer (NK) cells

components of adaptive?

• Humoral: Antibodies (B cells)

• Cellular: T cells (Helper & Cytotoxic)

What Is Innate Immunity

Innate immunity is the body’s immediate, non-specific response to infection.

what are some Anatomical Barriers of INNATE IS?

• Skin – mechanical barrier

• Mucous membranes

  • Mucus traps microbes

  • Cilia expel pathogens

• Acidic environments

  • Skin pH (~3–5)

  • Stomach acid

What are Physiological Barriers of innate IS ?

• Fever

• Normal body temperature

• Low pH

what are some Chemical Barriers of innate IS

• Lysozyme (breaks bacterial cell walls)

• Interferons

• Complement proteins

cellular mechanisms of innate IS ?

• Phagocytosis

• Endocytosis

Classical Signs of Inflammation ?

1. Rubor – redness

2. Tumor – swelling

3. Calor – heat

4. Dolor – pain

5. Functio laesa – loss of function (Virchow)

What Happens During Inflammation ?

• Vasodilation

• Increased vascular permeability

• Recruitment of phagocytes

• Clearance of pathogens and debris

what are PRR’S and PAMP’s and what’s an example of these to interacting?

• PRRs (Pattern Recognition Receptors) Receptors on innate immune cells that detect pathogens

• PAMPs (Pathogen-Associated Molecular Patterns) microbial structures not found in host cells (e.g pathogens)

Classic Example

• TLR4 (PRR) detects LPS (PAMP) from Gram-negative bacteria

what is genetic evidence of TLR4 and LPS inerractions

• Mutations in TLR4 gene causes :

  • Impair LPS signalling ( The body has trouble noticing the “bad bacteria” signal. )

  • Makes the body less sensitive to bacterial toxins.

  • Increases risk of getting sepsis (bacteria spreads to whole body)

Describe the MyD88 Pathway

1. TLR binds to PAMP on pathogen

2. MyD88 adaptor on TLR recruits IRAK1 + 4 Kinases

3. IRAK4 phosphorylates IRAK1 and TRAF6 Docs

4. IRAK1 and TRAF6 complex disassociates

5. TAK1 binds to IRAK1-TRAF6 complex to activate kinases

6. TAK1 can then activate NFkappaB + Map Kinase pathways which increases Transcription of inflammatory genes

main adaptor proteins?

• MyD88 (used by most TLRs)

• TRIF (important for antiviral responses)

How does Tak1 it activate NFkappaB pathway?

Tak1 activates IKK

which phosphorylates IKappaB

which activates NFkappaB

what are cytokines and interferons?

11. Cytokines & InterferonsCytokines

• what they are - cytokines are Small signalling proteins

• Secreted by immune and non-immune cells

• Control:

  • Activation

  • Proliferation (multiplying)

  • Differintiation

Interferons

• activates IS

• Promote infected cell death

• Recruit WBcells (for long lasting immunity)

describe the CYTOKINE SIGNALLING VIA JAK–STAT Signalling Pathway

1. Cytokine binds receptor + stabilises dimer

2. JAK domains come close to each other + activate (phosphorylate tyrosine residues)

3. STAT is phosphorylated by JACKs

4. STAT dimerises

5. dimer migrates to nucleus for Nuclear translocation

6. Gene transcription