Features and activation of phagocytes Flashcards Preview

Infection And Immunity > Features and activation of phagocytes > Flashcards

Flashcards in Features and activation of phagocytes Deck (37):
1

define Phagocyte

eating cell

2

define Phagocytosis

The uptake of large solid particles by the process of endocytosis

3

define Endocytosis

The uptake of extracellular material by invagination of the
plasma membrane to form vesicles enclosing the material

4

who discovered endocytes?

Ilya Ilyich Mechnikov's

5

Importance of phagocytes in innate immune system

1. Engulf pathogens and apoptotic or necrotic cells,
2. Release cytokines, e.g. to induce the Acute Phase Response in Macrophages

6

Importance of phagocytes in the Acquired immune system

1. Present antigens from these ingested particles to T cells (Macrophages and Dendritic cells only)

7

name 3 phagocytic cells?

Neutrophils, monocytes / macrophages,
and dendritic cells

8

whats the function of macrohphages?

phagocytosis and antigen presentation

9

whats the function of a dendritic cell?

antigen uptake in peripheral site and antigen presentation in lymph nodes

10

whats the function of a neutrophil?

phagocytosis and activation of bactericidal mechanisms.

11

whats the action of neutrophils?

1. Most important cellular component in bacterial destruction
2. 60% to 70% of circulating white blood cells (WBCs)
3. Max 24 hours (1/2 life = 7 hours)
4. response to inflammatory stimulus
5. Lobed nucleus and cytoplasmic granules (lysosomes)

12

what are Mononuclear phagocytes?

monocytes/macrophages

13

whats the prevalence of Mononuclear phagocytes?

1. 3 to 8% of circulating WBCs
2. Monocytes spend 1-2 days in blood, then go to tissues and become macrophages
3. Secrete biologically active compounds that regulate the immune system (e.g. cytokines)
4. Present antigens to T-lymphocytes

14

what are the key differences between neutrophils and macrophages?

1. N- hrs M- years
2. N- 1st new arrivals at inflamed sites M-Arrive later
3. N- Not present in healthy tissue
recruited to sites of inflammation M- Present in healthy
4. N- Dedicated phagocytes
M-Phagocytosis, Antigen presentation,Secrete proteins


15

where does a Monocyte differentiate into a Macrophage?

in tissue

16

name 4 types of macrophage

Alveolar Macrophage (Lungs)
Microglial Cell (Brain)
Kupffer Cell (Liver)
Langerhans Cell (Skin)



17

what happens to Phagocytes at sites of infection?

1. Initially PMNs most prevalent form of phagocyte
2. Monocytes move in and differentiate to macrophages
3. Both eventually die (PMNs die rapidly) due to ingestion of microbes and damaged tissue, forming pus
4. Pus formation especially notable with PYOGENIC bacteria (Greek, Pyon = Pus), e.g. Staphylococcus, Streptococcus, Neisseria

18

what the affect of Salmonella on neutrophils?

induces infiltration of neutrophils into the gut lumen

19

what are the Stages of Phagocytosis?

1. CHEMOTAXIS- phagocytic cell attracted to infection - microbial products, components of WBC or damaged tissues, complement
2. ADHERENCE- attachment of phagocyte to organism, may require OPSONISATION
3. INGESTION- involves pseudopods, fusion of pseudopods results in internalization in a specialized vacuole - PHAGOSOME
4. DIGESTION- phagosome fuses with lysosome, creating PHAGOLYSOSOME. Produce lytic enzymes to digest bacteria (lysozyme, proteases, nucleases, lipases), also superoxide anion, OH -, and H2O2
5.Undigestible material forms RESIDUAL BODY, migrates to plasma membrane Fusion releases waste materials, recruits other phagocytes

20

How do phagocytes recognise microbes
in order to phagocytose them?

1. Microbes recognised directly by characteristic surface components.
2. Microbes recognised indirectly if opsonised

21

how do phagocytes Directly recognise microbes?

1. via Pattern Recognition Receptors (PRR) on phagocyte e.g. Mannose-receptor, scavenger receptors, also certain Toll-like receptors
2. These PRR recognise conserved chemical components termed Pathogen Associated Molecular Patterns (PAMPs) on surface of microbes and trigger activation and phagocytosis

22

define OPSONISATION

a process that facilitates phagocytosis by coating antigens with an opsonin

23

who discovered Opsonin?

George Bernard Shaw 1856-1950

24

what are Opsonins?

- Opsonins are soluble Pattern Recognition Receptors (PRR)
- They bind a variety of microbial surface molecules which are important in microbial viability conserved during evolution
- Lipopolysaccharide (LPS), Liptoteichoic acid (LTA), Mannose (a microbial sugar molecule)

25

what are the most important opsonins?

1) IgG antibodies

2) Complement factor C3b

3) Acute phase proteins:
e.g. C-Reactive protein (CRP), Mannose-Binding Lectin (MBL), Collectins (SP-A, SP-D)

26

how do IgG Receptors work?

1. Fab-region reacts with organism
2. Fc domain reacts with Fc R on phagocyte

27

how do Complement receptors work?

1. CR3 and CR4 Found on both monocytes/macrophages and neutrophils
2. Both integrins, dimers of CD18 and CD11b = CR3 or CD18 and CD11c = CR4
3. Both bind C3b

28

what does CR3 (Mac-1) also recognise?

- The extracellular matrix - promotes adhesion
- ICAM-1 (CD54) on endothelial cells (CD18 required for phagocyte movement into tissues)
- Some surface structures on microorganisms - ie CR3 can sometimes bind in ABSENCE of opsonin

29

what are Acute Phase proteins?

c- reactive protein, MBL

30

what affect does C-reactive and MBL proteins have?

binds phosphorylcholine on bacterial surfaces acting as a opsonin activating compliment.

31

What effect does activation have on phagocytes?

Macs and neutrophils:
Increased phagocytosis + killing of phagocytosed microbes

Macs only:
Increased cytokine release, antigen presentation, expression of co-stimulatory molecules

32

What activates macrophages?

require two stimuli for full activation
Cytokines
e.g. IFN (from TH1 cells) - important
TNF
Chemokines
e.g. CCL2 (MCP-1)

Microbial compounds recognised by
Pattern Recognition Receptors
e.g. TLRs, Mannose Receptor etc

T cells (via CD40 L)

33

Surface molecules on monocytes- Involved in activation

1. CD14 (receptor for lipopolysaccharide (LPS) binding protein)
2. CD40
3. IFNg Receptor
4. Mannose receptor (mediates phagocytosis of microbes)
5. Scavenger receptors (bind bacterial and yeast cell wall carbohydrates or lipids)
6. TLRs (1-10)
7. Chemokine receptors

34

what are the responses of activated macrophages?

1. increased expression of co-stimulators
2. Killing of phagocytosised microbes
3. secretion of cytokines
4. increased expression of MHC

35

whats the role of Production of reactive oxygen intermediates nitric oxide; increased lysosomal enzymes?

Killing of microbes in phagolysomes (effector function of macrophages)

36

whats the roles of secretion of cytokines by macrophages?

TNF-a, IL-1: leukocyte recruitment (Inflammation)
IL-12: TH-1 differentiation,
IFN-g production (induction of response)

37

what the immunological role of Increased expression of:
CD80, CD86 (B7)
Class I, Class II MHC

Increased T cell activation (amplification)