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15 Cards in this Set

  • Front
  • Back
Complement System
- set of 9 blood proteins that enhance function of both adaptive and innate responses of infection
Antimicrobial Properties of Complement Proteins
1. Opsonization (C3b)
2. Lysis of bacteria (forms pore on bacterial membrane)
3. Amplification of inflammatory responses (anaphylatoxins C5a and C3a --> incr vasc permeability, chemotaxis, attract --phils)
Classic Pathway
1. C1 recognizes Ag-AB (with IgM and IgG) complex thru Fc and binds to it

2. This Ag-Ab + C1 complex cleaves C4+C2 complex = C3 convertase (C4b24b)

C3a (C4a and C2a) are released as anaphylatoxins

3. This C3 convertase complex binds to cell membrane and cleaves C3 into C3a and C3b

4. C3 convertase splits many C3 mcls --> amplification

5. C3b + C3 convertase bound to cell membrane (C4bC2b)= C4b3b2b (C5 convertase)

6. C5 convertase then splits C5 into C5a and C5b fragments

7. C6, C7, C8, and C9 then attach = C5-C9 membrane attack complex

--> C5bC6C7C8 + many C9s

8. Bacteria lyses/disentigrates
Anaphylatoxins: what do they do and what are they?
C3a and C5a:

- incr permeability: leaky capillaries
- induce muscle contraction (degranulation)
- induce mast cells to release histamine (allergic rxn, kills parasites)
- chemotaxis of neutrophils and monocytes out of capillaries into tissues

C3b is also an opsonin, so enhances phagocytosis bc phag cells have receptor for it
Complement Pathway
- NO AB COMPLEX REQUIRED

1. In presence of LPS, peptidoglycan, techoic acid- C3 is hydrolysized

2. C3b on surface of bacterial cells is recognized by Factor B

3. Factpr D cleaves Factor B = C3bBb, release of Ba

4. C3bBb is recognized by Properdin, which stimulates C3 convertase (C3bBbP)

5. C3 convertase cleaves and activates many C3 mcls --> amplification and C5 convertase

6. C3bBbP3b (extra 3b from addition of another activated C3b)

7. C5-C9 form MAC

8. Cell lysis and bursts
C3 and C5 Convertase For Classic and Alternative
Classic:

C3: C4b2b
C5: C4b2b3b

Alternative:

C3:C3BbP
C5: C3bBbP3b
How are bacteria killed by complement/MAC?
MAC forms a pore on bacterial cell membrane

K+ and Cl- flow out

H2O and Na+ flow in

Cell lysis
Defensins: what and who has?
small cyesteine rich proteins found in inverts and verts

active vs. bact, fungi, and env and non enveloped viruses

cells in immune system have these peptides to aid in killing phagocytosed bact (ex. in neutrophils and almost all epithelial cells)

bind to microbial cell membrane and form pore like membrane defects that llow efflux of essential nutrients

PORE: LEAK AND LYSE
Defensins: main function?
penetrate bacterial cell membrane and lyse bact cells

forms pore like structure allowing efflux of K and Cl and influx of Na and water
chemokines
low molec weight proteins that stimulate leukocyte (WBC) movement/chemotaxis

blood --> tissue
cytokines
proteins that act thru specific receptors

regulate and activate immune responses
cytokines important for inflammation
IL-1 : induces fever --> hypothalamus, incr T --> most pathogens cannot multiply well, but immune cells can

TNF: tumor necrosis factor alpha
Inflammation and Heart Disease
incr. of C reactive protein in response to inflammation

activates complement chain
Coronary Heart Disease
most common disease of heart

characterized by hardening and narrowing of coronary arteries due to plaque build up = artherosclerosis

plaque: cholesterol and other lipids

blood flow and oxygen supply to heart can be reduced or even fully blocked with growing plaque

plaques may rupture and cause clots that block arteries
Process of artherosclerosis
oxidized LDL binds to endothelial cell, lining and damaging vessel walls

macrophages engulf but cannot breakdown -->full and lyse