Week 1: Innate Immune system and 10 exam like questions

What are the main differences between the innate and adaptive immune system?

• Innate: is bodys 1st repsonder, fast, non-specific, no memory, includes a barrier, have phagocytes, Nk cells and the complemet system

• Adaptive: slow (days), highly specfic, has a memory, involves T-cells & B-cells

Which immune system forms a memory response?

The adaptive immune system through through T-cell and B-cells

Which 2 cells are responsible for the adaptive immunity ?

1. T-lymphocytes (T- cells)

2. B-lymphocytes (B-cells)

How can the complement system become actiavted?

via 3 pathways

1. Classical Pathway - antibody-antigen complex
2. Lectin pathway - mannose-binding lectin bind to microbial sugar
3. Alternative pathwys - Spontaneous activation on microbial surfaces

Describe how the classcical pathway is activated 

1. the classical pathways is triggered when the antibody binds to an antigen (bacteria)

2. C1s cleaves C4 into C4A + C4B

3. C4B = binding to the pathogen

4. C4A floats away (inflammation)

5. C2 binds to C4B then C1s cleaves C2

6. into C2A and C2B

7. C2A + C4B = C3 convertase (C4BC2A)

8. this cleaves C3 into C3A +C3B

describe the lectin pathway

1. MBL (mannose-binding lectin) or Ficolin’s remember mannose sugar on the surface of microbes

2. MBL is like a sensor, so when it binds to mannose, it activates MASP-1 & MASP-2 (Mannose-binding lectin-Associates serine proteases )

3. MASP-2 cleaves C4 into C4A+C4B

4. C4B binds to a pathogen whist C4A float away

5. MASP-2 cleaves C2 into C2A + C2B

6. C4B binds to C2 and MASP-2 cleaves C2 bound to C4B 

7. C2A joins C4b = C3 Convertase of lectin pathway

8. C3(C4BC2A) cleaves C3 into C3A +C3B

describe the alternative pathway

1. when a bacteria cell wall is not protected, C3 can stick & start a cascade

2. C3B binds to Factor B

3. the D factor then cleave factor B making Bb resulting in 3bBb = C3 convertase of alternative pathway

4. C3bBb cleaves to c3a + c3b

5. this generates alot of C3b to stick onto a pathogens surface which hugs the amplification loops

What are the 3 main outcomes of the complement activation

1. opsonization - C3b coats pathogens for phagocytosis

2. Chemotaxis - C5a attracts immune cells

3. Cell lysis - Membrane Attack Complex (MAC) forms pores in pathogens 

How is the Mebrane Attcak Complex (MAC) formed?

• the complement proteins C5b, C6, C7, C8 and multiple C9 molecules form into a pore that inserts into the pathogens membrane, which causes lysis.

What components make up the complement system

• over 30 proteins including C1-C9, factors B,DP and regulatory proteins

What is the role of the Natural Killer (NK) cells

• its kills the virus- infected cell and tumor cells without prior sensitisation

How do NK cells decide whether to kill a target?

• inhibitory receptors bind self MHC Class I - "dont kill"

• If MHC I is missing (viral infection) or altered , the inhibtory signal is lost

• activating receptors bind to the stress ligand which trigegrs killing

What happens if MHC Class I is missing from a cell

• when NK inhibtory receptors are no engaged it actiavates signal calling thr NK cells to kill the cell

What happens during Phagocytosis

1. Recognition: pathogen is recognised by receptor

2. Engulfment: Membrane engulf pathogen forming a phagosome

3. Fusion: Phagosome fuses with Lysosome forming phagolysome

4. Destruction: the digetsive enzyme & ractive oxygens degrade the pathogen

What is the role of Type I inteferons (IFN- a/b)

• it inbits viral replication

• increases MHC I expression on cells

• ACtivated the NK cells

• and induces antivral state in neighboring cells

How does the IFN- JAK- STAT pathway work?

1. IFN binds to the receptor 

2. Actiavting the JAK kinases

3. STAT proteins are then phosrylated, dimerized and translocated to the nucleus 

4. this cause a induced transcription of antiviral genes (oligoadenylate , P1 Kinase, Mx

What are the 5 cardinal signs of inflammation

1. Rubor (Redness)

2. Calor (heat)

3. Tumor (swelling)

4. Dolor (pain)

5. Function laesa (loss of function)

What 4 cells triggers vasodilation in inflammation?

1. Histamine
2. Kinins
3. Protaglandins
4. Leukotreines

These are released by damaged cells & immune cells 

what is margination and diapedesis

• margination: is when leukocytes bidn to endotheial cell lining blood vessels

• Diapedessi: is when leukocytes squeeze between endothelial cells to enter tissues

What are the main stages of inflammtion

1. Vasodilation - redness, heat, swelling

2. Migration & margiantion - leukocytes enter the tissues

3. Pagocytosis - pathogen are destroyed

4. Tissue repair - debris is cleared and healing begins

list 6 soluble factors involved in innate immunity

1. Lysozome

2. defensins

3. cytokins

4. chemokines

5. complememt proteins

6. prostaglandins

How are prstaglandins synthesised 

From arachidonic acid via cyclooxgenase (COX-1 and COX-2) enzymes

What is role of prostaglandins in inflammations?

Cause vasodilation, fever, and pain which increases imflammatory response

How do NSAIDs like aspirin and ibuprofen work?

• They inhibts COX enymes which reduce prostaglandin synthesis which redices inflmmation, fever and pain

Why does inflammation happen? 

inflammation occurs to eliminate pathogens, limit tissue damage and initiate repair

why do immune cells migrate into tissue during inflammation 

because they are chemicall called to the site of infection/injury by chemokine and cytokine to destroy pathogens, clean up debris and start repair