Innate Immunity

Question 1

Adaptive Immune response consists of

the production of…

Answer 1

antibodies and specific

subsets of T cells

Question 2

What do invertebrates have only?

Answer 2

innate

Question 3

Recall some components of innate immunity(5)

Answer 3

•	Phagocytes- Macrophages/Dendritic cells/granulocytes/neutrophils
•	Inflammation
•	Cytokines/chemokines
•	Complement
6. Natural Killer cells

Question 4

What is inflammatory response?

Answer 4

• A generic defence mechanism whose purpose is to localize and eliminate injurious agents and to remove damaged tissue components

Question 5

What does inflammatory response enhance?(4)

Answer 5

• Enhanced permeability and extravasation
• Neutrophil recruitment
• Enhanced cell adhesion
• Enhance clotting

Question 6

What triggers inflammation?

Answer 6

• Triggered by the release of pro-inflammatory cytokines and chemokines at the site of infection

Question 7

What are cytokines?(2)

Answer 7

• Act to modify the behaviour of cells in the immune response
• Most of these are called interleukins (eg. IL-1)

Question 8

What are interleukins?

Answer 8

Names for cytokines

Question 9

What are chemokines?

Answer 9

• Act as chemotactic factors – i.e. they create concentration gradients which attract (or occasionally repel) specific cell types to a site of production/infection

Question 10

Name some receptors found on macrophages

Answer 10

mannose receptor

2. complement receptor
3. scavenger receptor
4. dectin- b glucan receptor

Question 11

What are PAMPs?(3)

Answer 11

• Molecules present only on pathogens and not on host cells

2. • Essential for survival of pathogens
3. • Invariant structures shared by entire class of pathogens

Question 12

What are the structures found on gram negative cell surface?

Answer 12

lipopolysaccharides (LPSs) found in outer membrane

Question 13

What are the structures found on gram positive cell surface?(3)

Answer 13

teichoic acid,
lipoteichoic acid,
3. peptidoglycan found in outer membrane(cell wall)

Question 14

Name so other PAMPs?

Answer 14

• Bacterial flagellin
• Abnormal protein glycosylation
• Abnormal nucleic acids – viruses

Question 15

What are PRRs?

Answer 15

• Host factors that specifically recognise a particular type of PAMP
• They are germ-line encoded

Question 16

Recall the three classes of PRRs

Answer 16

o Extracellular – they recognise PAMPs outside of a cell and trigger a co-ordinated response to the pathogen

o Intracellular (cytoplasmic) – they recognise PAMPs inside a cell and act to co-ordinate a response to the pathogen

o Secreted – they act to tag circulating pathogens for elimination

Question 17

What are interferons?

Answer 17

• Interferon(cytokines) binds to receptors on other cells which triggers the production of about 400 enzymes
• The enzymes create a hostile environment for any virus that is trying to replicate.

Question 18

What is the complement system?(2)

Answer 18

• A system of secreted proteins made in the liver that recognise PAMPs on the surface of microbes and “decorate” or “tag” them.

2. The microbes are then cleared by phagocytosis, “opsonised” or they have holes punched in them.

Question 19

Where are interferons secreted from?

Answer 19

the liver

Question 20

What are the three ways of activating the complement system

Answer 20

• (i). Recognition of LPS and other PAMPs by the C1q component of “classical” pathway
• (ii). Non-host glycosylation is recognised by MBP(mannose binding protein/lectin) and other lectins to activate the “lectin” pathway
• (iii). Membranes that are recognised as “non-self” activate the “alternative” pathway

Complement activation involves a proteolytic cascade

Question 21

What do natural killer cells do?

Answer 21

• NK cells possess the ability to recognise and lyse virally infected cells and certain tumour cells.

2. • Selectivity is conferred by LOSS of “self” MHC molecules on target cell surfaces, AND up-regulation of activating ligands

Question 22

What percentage of WBCs as NKs

Answer 22

• 4% white blood cells

Question 23

Describe the structure of NKs

Answer 23

• Lymphocyte-like but larger with granular cytoplasm

Question 24

What causes target cell destruction?

Answer 24

caused by cytotoxic molecules called granzymes & perforins

Question 25

What are some diseases that can be caused by defects in the complement system?(2)

Answer 25

1. core defects(C3) causes autoimmune diseases such as lupus

2. non-core defects linked to susceptibility to specific types of pathogens such as Neisseria

Question 26

What disease can arise from macrophage deficiency?

Answer 26

Chronic granulomatous disease (CGD); No oxidative burst for bacterial killing

2. IRF8 mutations linked to susceptibility to TB

Question 27

What is a syndrome that can arise from constitutive production of inflammatory cytokines?

Answer 27

• Aicardi–Goutières syndrome

Question 28

• Lack of interferon-responsiveness causes…

Answer 28

sensitivity to viral infection (e.g. measles)

Question 29

Compare innate and adaptive response

Answer 29

Innate:
macrophages, neutrophils, Dcs
2. fast
3. no memory required
4. receptors are pattern recognition
5. PAMPs

Adaptive:
lymphocytes
2. slow
3. memory cells
4. receptors are Immunoglobins and TCR
5. billions of possible antigens

Question 30

what is IL-1?

Answer 30

→Main producer = Macrophages + keratinocytes
→Acts upon = lymphocytes + liver
→Effect = Enhances response
→ Induces acute-phase protein secretion

Question 31

what is IL-6?

Answer 31

→ Main producer = Macrophages + dendritic cells
→ Acts upon = lymphocytes + liver
→ Effect = Enhances response
→ Induces acute-phase protein secretion

Question 32

what is CXCL8 (IL-8)?

Answer 32

→Main producer: Macrophages + dendritic cells
→Acts upon: Phagocytes
→Effect: Chemoattractant for neutrophils

Question 33

what is IL-12?

Answer 33

Main producer: Macrophages + dendritic cells
→ Acts upon: Naive T cells
→Effect: Diverts immune response to type 1, →proinflammatory, cytokine secretion

Question 34

what is TNF - alpha?

Answer 34

Main producer: Macrophages + dendritic cells
→Acts upon: Vascular endothelium
→Effect: Induces changes in vascular endothelium (expression of cell-adhesion molecules (E- + P- selectin), changes in cell-cell junctions w/increased fluid loss

Question 35

how do macrophages “see” microbes?

Answer 35

→Passive sampling
→ Scavenger receptors
→Engulfing apoptotic cells

Question 36

Lectin receptors

Answer 36

→Ligand: terminal mannose and fucose

→Outcome: phagocytosis

Question 37

Scavenger receptors

Answer 37

→Ligand: bacterial cell walls modified low-density lipoproteins
→Outcome: phagocytosis

Question 38

Toll-like receptors (TLRs) (surface and endosomal)

Answer 38

→Ligand: LPS (together with CD14) lipoproteins unmethylated CpG flagellin ds RNA; ss RNA (in endosomes)

→Outcome: inflammation: cytokine release (TNF, IL-1, IL-12) enhanced killing: reactive oxygen species, NO)

Question 39

NOD-like receptors (NLRs) (cytoplasm)

Answer 39

→Ligand: peptidoglycan from Gram positive and negative bacteria some viral DNA and RNA (indirect?)

→Outcome: inflammation: cytokine release (IL-1, IL-8)

Question 40

RIG-like receptors (RIG-1 and MDA5) (cytoplasmic)

Answer 40

→Ligand: dsRNA and 5’-triphospho RNA

→Outcome: type I interferon production

Question 41

how does cell death happen?

Answer 41

→Perforin + cytotoxic granules

→Engagement of death receptors

Question 42

NK cells bind

Answer 42

cells bind HLA-E which carries in its groove a peptide from the leader sequence of classical class I MHC molecules

Question 43

CMV (Cytomegaloviruses ) has four gene products which

Answer 43

→reduce the expression of Class 1 MHC molecules and two class I MHC homologues (UL18 & M144), that give a negative signal to NK cells