Immunology 3: Innate Immunity Flashcards

1
Q

What are the 3 recognition stratergies

A

Detect conserved microbial structures - PAMPs

Detect metabolic consequences of cell infection or injury - DAMPs

Detect ‘missing self’

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2
Q

4 innate immunity defensive barriers

A

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

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3
Q

7 Cell types in innate immunity

A

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

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4
Q

Describe neutrophils

A

(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

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5
Q

Describe macrophages

A

less abundant,

dispersed throughout the tissues;

signal infection by release of soluble mediators

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6
Q

What 3 things do neutrophils do to fight infection

A

Bind pathogen

Phagocytose pathogen

Kill pathogen

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7
Q

Describe the Movement of Neutrophils into Tissues:

A

Low affinity bidning to selectins at the start if the tissue

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

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8
Q

What is diapedesis

A

movement of a cell across the endothelial layer

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9
Q

What is opsonisation

A

coating of micro-organisms with proteins to facilitate phagocytosis

Opsonins act as adapter molecules which bind to the pathogen and link it to receptors present on the phagocyte.

Antibodies and Complement Proteins act as opsonins. - which then bind to phagocytes

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10
Q

What are the two neutrophil killing mechanisms

A
Oxygen-Independent 
Enzymes 
Lysozyme 
Hydrolytic Enzymes 
Antimicrobial Peptides (Defensins) 

Oxygen-Dependent

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11
Q

What are NEUTROPHIL EXTRACELLULAR TRAPS (NETs)

A

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.

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12
Q

2 Function of macrophages

A

phagocytosis

signal infection by releasing soluble mediators (alarm cytokines).

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13
Q

Describe Mast cells

A

Not in blood-> in tissues

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

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14
Q

Describe natural killer cells

A

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)

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15
Q

Describe target cell recognition in natural killer cells

A

Missing self recognition

target cells have MHC class I markings on the cell
these are inhibitory to NK cells
If theres a problem with the cell these markings might not be present

Induced self recognition

Target cells have stress-induced molecules on its surface if theres a problem
these activate the NK cells

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16
Q

Describe cytokines

A
small secreted proteins
cell-to-cell communication
“messengers” of the immune system
generally act locally
biological effects at very low concentrations
short-lived
17
Q

5 Types of Cytokine

A

Interleukins (IL-x) - between leukocytes

Interferons (IFN) - anti-viral effects

Chemokines - chemotaxis and movement

Growth Factors

Cytotoxic - tumour necrosis factor (TNF)

18
Q

What do dendrites do

A

Antigen presenting cell

recognise pathogens and secrete cytokines

19
Q

What is the complement system

A

‘Complements’ the activity of a specific antibody

Triggers enzyme cascade

20
Q

Three main ways of complement activation

A

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

21
Q

What do the compliment activation pathway converge to

A

c3-Activation of C3 is a common final pathway which leads to the formation of MEMBRANE ATTACK COMPLEX (MAC) which is what lyses infected cells or bacteria.

22
Q

Control of compliment activation pathway (3)

A

Components have very short half lives

Complement is diluted in body fluids

There are specific regulatory proteins which help regulate the activity of complement
(e.g. CD59 is expressed by many normal cells to make them resistant to complement mediated lysis)

23
Q

4 Functions of complemet

A

lysis

Opsonization

Activation of inflammatory response

clearance of immune complexes

24
Q

What does complement system activation lead to

A

production of pro-inflammatory fragments (anaphylatoxins)

Anaphylatoxins bind to receptors on mast cells
they will degranulate
affects vascular permeability
increased adhesion of circulating leukocytes.

Some of the products of degranulation are directly chemotactic for neutrophils.

25
Q

What is the systemic acute-phase response

A

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

26
Q

What are 4 acute phase protien

A

C-reactive protein (CRP)
C polysaccharide of pneumococcus
Activates complement
Level may increase 1000 fold

Mannan-Binding Lectin (MBL)
Opsonin for monocytes
Activates complement

Complement

Fibrinogen
Clotting