3-innate Immunity

Question 1

What are some features of innate immunity?

Answer 1

inbuilt”, present from birth
•not enhanced by second exposure (has no memory)
•uses cellular and soluble components
rapid response, minutes to hours, cooperates
with and directs adaptive immunity

Question 2

What are some innate immunity defensive barriers ?

Answer 2

Anatomical (physical):
Skin - mechanical barrier, acidic environment
Mucous membranes - mucus secretions trap microorganisms, cilia (respiratory tract) expel microorganisms

Physiological:
Body temperature / fever
Low pH - acidic pH of stomach kills many ingested microorganisms
Chemical mediators - lysozyme, interferons, complement

Phagocytic: cells ingest material

Inflammatory: local vascular permeability increases

Question 3

What are the cell types of innate immunity?

Answer 3

Neutrophil: phagocytosis and killing of microbes
•Eosinophil: phagocytosis, granule release, defence against parasitic infections, help B cell responses in GALT (IgA production)
•Basophil: granule release, may act as APC for “type 2 immunity”
•Monocyte / macrophage: phagocytosis, killing, cytokine release, act as APC
•Mast cell: granule release (pro-inflammatory)
•Dendritic cell: antigen capture and presentation
•Natural killer cell: lysis of infected cells

Question 4

Describe the phagocytic cell types

Answer 4

neutrophil (polymorphonuclear leukocyte) 40-75% of leukocytes; short lived cells, circulate in blood then migrate into tissues; first cells to be recruited to a site of tissue damage/infection

•macrophage less abundant, dispersed throughout the tissues; signal infection by release of soluble mediators

Question 5

How do neutrophils move into tissues

Answer 5

diapedesis and chemotaxis:
Similar to movement of lymphocytes into lymph nodes
• Near the site of infection there will be some damage or maybe a macrophage becomes activated
• Chemokines are released which bind to the local endothelial layer
• Chemokines are only present on the endothelial surface if there has been an infection (they aren’t naturally there).
• Neutrophils will roll along the surface with low affinity interactions (binding to selectin).
• Integrin will be in the low-affinity state.
Integrin activation by chemokines - chemokine receptor on neutrophil binds to chemokine on endothelial surface and activates integrin converting it to the high-affinity state.
• Stable Adhesion - Integrin binds STRONGLY to the integrin ligand and the neutrophil is immobilised
• Cells migrate into tissue - the cells then follow a chemokine gradient to figure out where to go - this is chemotaxis

Question 6

Give examples of PAMPs

Answer 6

Bacteria - flagellin, peptidoglycan, glycolipids, lipoproteins
• Virus - ssRNA, dsRNA, envelope -
• Fungus - unmethylated CpG motifs
• Parasite - Glycolipids, DNA

Question 7

Give examples of DAMPs

Answer 7

Cell - high extracellular ATP, DNA

• ECM - fragments from collagen, hyaluronan, aggrecan

Question 8

What are the 2 main opsonins?

Answer 8

Antibodies

Complement Proteins

Question 9

What are some neutrophil killing mechanisms?

Answer 9

oxygen-independent
–enzymes
–lysozyme
–hydrolytic enzymes
–antimicrobial peptides (defensins)
•oxygen-dependent
–respiratory burst:
–superoxide anion
–hydrogen peroxide
–singlet oxygen
–hydroxyl radical
–reactive nitrogen intermediates
–nitric oxide

Question 10

What are NETs?

Answer 10

NEUTROPHIL EXTRACELLULAR TRAPS (NETs)
• When neutrophils become highly activated they release these nets that help trap extracellular bacteria and immobilise them.
• This helps other cells find these trapped bacteria.

Question 11

Describe mast cells

Answer 11

secrete histamine and other inflammatory mediators, including cytokines
•mucosal mast cells (lung)
•connective tissue mast cells (skin and peritoneal cavity, near blood vessels)
•can recognise, phagocytose and kill bacteria
•can be activated by complement products (anaphylatoxins)
•leads to vasodilation and increased vascular permeability

Question 12

Describe

NK cells

Answer 12

large granulated lymphocytes: cytotoxic, lyse target cells and secrete the cytokine interferon-
•5-10% peripheral blood lymphocytes
•no antigen-specific receptor, but express both activating and inhibitory receptors: balance of signals
•have receptors which bind to antibody-coated cells (Antibody Dependent Cell-mediated Cytotoxicity)
•important in defence against tumour cells and viral infections (esp. herpes)

Question 13

What are cytokines?

Answer 13

Small secreted proteins
• Involved in cell-to-cell communication
• 'Messengers' of the immune system
• Powerful biological effects at low concentrations
• Short-lived

Question 14

What are the types of cytokine?

Answer 14

Interleukins (IL-x) - between leukocytes
• Interferons (IFN) - anti-viral effects
• Chemokines - chemotaxis and movement
• Growth Factors
• Cytotoxic - tumour necrosis factor (TNF)

Question 15

What are Important cytokines secreted by activated macrophages?

Answer 15

• IL-1: alarm cytokine, FEVER
• TNF-α : alarm cytokine
• IL-6: acute phase proteins, acts over long distances,
• IL-8: chemotactic for neutrophils
• IL-12: directs adaptive immunity, activates NK cells

Question 16

Describe the complement system

Answer 16

Plays a major role in complementing the activity of specific antibody
•complex series of ~30 proteins and glycoproteins, total serum conc. 3-4 mg/ml
•triggered enzyme cascade system
•rapid, highly amplified response
•components produced mainly in the liver, but also by monocytes and macrophages

Question 17

What are the 3 complement activation pathways?

Answer 17

The Classical Pathway
–initiated by antigen-antibody complexes
•The Alternative Pathway
–direct activation by pathogen surfaces
•The Lectin Pathway
–antibody-independent activation of Classical Pathway by lectins which bind to carbohydrates only found on pathogens

Question 18

How can Dendritic Cells also recognise pathogens and secrete cytokines?
•

Answer 18

Dendritic cells are located at sites of likely infection
• Phagocytose
• Can recognise PAMPs - so can be considered part of innate immunity
• Migrate once they’ve captured the antigen to the lymph nodes to activate T
lymphocytes
• Direct link between acquired and adaptive immunity
• Produce cytokines once they have been activated

Question 19

What is an acute phase response?

Answer 19

local inflammatory response may be accompanied by a systemic response, “acute phase” after 1-2 days
•fever, increased production of white blood cells (leukocytosis), production of “acute-phase” proteins in the liver
•induced by cytokines

Question 20

Name 4 acute phase proteins

Answer 20

C-reactive protein (CRP)
–C polysaccharide of pneumococcus
–activates complement
–level may increase 1000 fold
•mannan binding lectin (MBL)
–activates complement
•complement
•fibrinogen (clotting)