L03: Innate immunity overview

Question 1

Layers of immunity (3)

Answer 1

1. Barrier defence: epithelium and host defence
2. Innate immunity: cellular mediators of innate immunity, connectedness with adaptive immunity, leukocyte recruitment, soluble mediators of innate immunity
3. Adaptive immunity

Question 2

Pathogen

Answer 2

Biological agent causing disease or an organism that breaches the host innate immune system

Question 3

Innate immunity danger senses (2)

Answer 3

Through cellular mediators and soluble mediators

Question 4

Sensing something not present on self

Answer 4

1. Pattern recognition receptors detect PAMPs (cellular mediators)
2. Classical and MBL complement activation (soluble mediators)
3. Activating signal allows microbial destruction

Question 5

Sensing absence of something normally present on self

Answer 5

1. NK cell activation (cellular medaitors)
2. Alternative complement activation (soluble mediators)
3. Inhibitor signal prevents host destruction

Question 6

Barrier layer

Answer 6

First line and non specific: microbes encounter external coverings and their secretions

Question 7

Innate layer

Answer 7

Second line and non specific: microbes penetrating barriers encounter phagocytes and inflammation

Question 8

Adaptive (acquired) layer

Answer 8

Third line and specific: surviving microbes encounter cell-mediated and humoral responses

Question 9

Differences in innate VS adaptive

Answer 9

Timing
Specificity
Memory

Question 10

Epithelium

Answer 10

Tissue containing layers of cells lining outside (skin) and inside cavities and structures in the body. Functions for exchange of nutrients, gas water products, and in immune response: physical barrier to prevent microbial entry; mechanical function; chemical; microbiological; express PRRs

Question 11

Cellular and soluble mediators

Answer 11

Cellular and soluble mediators destroy the microbe and trigger inflammation, acting in synergy
Soluble mediators can be made or performed by cellular mediators in response to infection

Question 12

PRRs and PAMPs

Answer 12

Pattern recognition receptors to recognise microbial structures = pathogen-associated molecular patterns; initiate inflammatory response

Question 13

Myeloid cells (6)

Answer 13

1. Neutrophil - phagocytosis and activation of bactericidal mechanisms
2. Eosinophil - killing of antibody-coated parasites
3. Basophil
4. Mast cell - release of granules containing histamine and other active agents
5. Macropage - phagocytosis and activation of bactericidal mechanisms
6. DCs - antigen uptake in peripheral sites, antigen presentation in LN

Question 14

Lymphoid cells

Answer 14

NK cells - relelase lytic granules that kill some virus-infected cell
Innate lymphoid cells (ILCs): lymphoid-derived cells, roles in pathogen clearance and inflammation

Question 15

Mechanisms of leukocyte recruitment (4)

Answer 15

1. Rolling adhesion
2. Firm adhesion
3. Diapedesis
4. Migration

Question 16

Rolling adhesion

Answer 16

Infection triggers chemokine release and upregulation of selectins on endothelial cells. Selectins are receptors which bind carbohydrates on leukocytes and are part of the initial adhesion step

Question 17

Firm adheson

Answer 17

Other molecules interact to enable leukocytes to tightly bind:

1) ICAM-1 (intracellular adhesion molecule) on endothelial cell weakly binds to LFA-1 (leukocyte functional antigen) on leukocyte
2. Chemokine on endothelial cell binds to chemokine receptor on leukocyte strengthening the bind

Question 18

Soluble mediators of innate immunity:

Answer 18

1. Anti microbial peptides: primarily produced by epithelial cells; direct anti-microbial action
2. Complement: system of plasma proteins; activated by alternative, lectin and classical pathways; direct anti-microbial activity, opsonins and chemoattractants
3. Cytokines and chemokines: secreted proteins from range of cell types that act locally and systemically; increase vascular permeability, leukocyte recruitment, acute phase response, body temperature, antigen presentation; enables recruitment and activation of leukocytes; chemokines are able to induce directed chemotaxis in nearby responsive cells
4. Other proteins: lysozyme (degrades peptidoglycan), calgranulins (anti-bacterial property neutrophil products); pentraxins (many functions)

Question 19

Complement system

Answer 19

Series of pre-formed proteins present in an inactive state in body fluids and tissues and enhances pathogen clearance. Important for cell recruitment, opsonisation, and direct killing of pathogen. 3 pathways of activation (classical, MB-lectin and alternative)

Question 20

Classical pathway

Answer 20

Ag/Ab provides trigger: Ab recognise Ag present on surface of microbes and cluster around

Question 21

Mannose-binding lectin pathway (MB-Lectin)

Answer 21

Sugars on pathogen surface provide the trigger: sense something that shouldn’t be there and trigger activation

Question 22

Alternative pathway

Answer 22

Slow tick-over of C3 enables binding of complex to cells: regulatory proteins on host cell prevent complement activation, inhibitory signal is lost so immune activation is triggered

Question 23

Key effectors in the complement system (3)

Answer 23

C5a - cell recruitment (chemoattractant)
C3b - opsonisation (reactive component which binds covalently to the pathogen surface, tagging it for macrophages and other immune cells)
C9 - pore of membrane-attack complex for direct killing of pathogen, forms pore in membrane of pathogen for lysis