First Responders to Infection

Question 1

how do macrophages interact with bacteria?

Answer 1

toll receptors etc.

Question 2

CR1

Answer 2

binds to c3b on macrophage

Question 3

TLR4

Answer 3

its on macrophage and recognized and binds LPS

Question 4

TLR5

Answer 4

on macrophage and binds and recog flagella

Question 5

mannose and macrophages

Answer 5

macro bind to mannose which is unique to bacteria and not on euk cells

Question 6

TLR9

Answer 6

macrophage recog dna motifs (the unmethylated) so when bacteria dies the macro can bind and activate to present to other cells and also deal with it itself

Question 7

PRR and PAMP r/t macrophage

Answer 7

TLR’s are on macro and are the PRR

PAMP are on the bacteria and are the ligands

Question 8

binding of macrophages signals what?

Answer 8

inc synthesis of cytokines and phagocytosis

Question 9

IL1B

Answer 9

pro inflame cytokine released by macrophage binding - activates vasc epithelium and inc access of effector cells - fever - inc production of IL 6

Question 10

TNF alpha

Answer 10

not pro inflame cytokine but released by macrophage binding and it also inc vasc permeability so IgG can come in and activate complement and inc lymph drainage

Question 11

IL6

Answer 11

pro inflame cytocyyke _ activates lymphocytes with macrophage binding and inc ab production

Question 12

IL12

Answer 12

not pro inflame but cytokine released with macrophage binding that activates NK cells and inc T cell proliferation and differentiation esp into helper Ts… inc ab response

Question 13

CXCL8

Answer 13

not pro inflame but cytokine released with macrophage binding and technically a CHEMOKINE that helps a cell follow a conc gradient from low to high and promote WBCs to go from blood back to where infection truly is.

Question 14

selectin

Answer 14

on epithelium of inner vasc wall. interacts with PMNs and WBCs - as they flow through the blood they attach and break and attach and break (rolling) to see if there is any abnormality or infection… signal molecular signals to make inflammation… if it does come across endothelial cells will change and induce addressins which is a cell adhesions molecule that attaches to a receptor on WBCS

Question 15

ICAM and LFA1

Answer 15

ICAM addresin molecule that attaches to a receptor LFA 1 (a leuk antigen) when a PMN attaches to a selection

when it binds to LF1 it makes tighbinding to epithelial cells and then CXCL8 acts on LFA1 to be even tighter bound to ICAM (via conformational change) -

the result of this is that the neutrophil is now stuck to capillary wall and will under go diapedisis through the endothelial wall and into tissue. once inside it interacts with more CXCL8. then it moves from down a gradient to where macrophages are and localizes to the site of infection.

Question 16

IL6 IL1 and TNF (cytokine) effect on liver, bone marrow, hypothalamus, dendritic cells

Answer 16

liver - acute reactive proteins - activate complement and opsin

bone marrow - neutrophil mobilization and phagocytosis

hypothalamus - inc body temp (along with fat and muscle)

dendritic cells - link innate to adaptive and TNF stimulates migration to lymph nodes and matureation

Question 17

Local effects of infection

Answer 17

1. macrophage secret TNF into tissue.
2. inc plasma prot and immigration into tissue. plots stick to cell walls
3. phag of bacteria. local vessel occlusion localizes and keeps infection in one place
   antigen carried to nearby lymph node to drain
4. adaptive immunity

Question 18

Systemic effects of infection

Answer 18

1. macrophages in liver and spleen secret TNF into blood
2. dec BP and collapse of BV
3. DIC - mods - death (SHOCK)

Question 19

serum amyloud protien

Answer 19

acute phase protein from liver - fxn not known

Question 20

mannen binding lectin/protein

Answer 20

acute phase protein from liver - bind to bacteria turn on complement and clotting factors. can also bind an opsin on a macrophage

Question 21

c reactive protein

Answer 21

acute phase protein from liver - activate cascade and act like an opson

Question 22

acute phase protein

Answer 22

from liver - inducted by release of cytokines - usually activates complement and opson

Question 23

IFN alpha and beta

Answer 23

type one interferons. its how the innate immune system reacts to a virus. they talk to neighbors. they increase MHC class 1 presenters so T calls can present more viral peptides. they activate NK cells so that they happen to BE ABLE TO SEE the cells that no longer make MHC to surface (how a virus tries to trick and protect itself once inside a cell and replicating ) - and then the NK kills.

alpha by leuk

beta by fibroblasts

Question 24

what is the antiviral response?

Answer 24

act of binding to INF receptor is the antiviral response

if bind to self it can help or if bind to others it will inhibit viral replication and break mRNA - inhibit growth too…. also it up regulates MHC expression so T cells can recog again/better.

Question 25

give an example of a viral mechanism involving MCH class I.

Answer 25

MHC is attached ion host cell by ADENOVIRUS and E3 blocks transport of MHC to surface - helps keep adaptive immunity from regonizeing cells infected

Question 26

how do innate and adaptive immunity work together to kill a viral infection? what if you lacked one or the other?

Answer 26

innate (interferrons and NK) help to limit growth of infection initially. then adaptive (T) knocks it out. at hight of innate response the viral load flattens out/plateuas. results in clearance of infection ultimately.

if you lack innate you will have a virus grow out of control by the time adaptive can kick in

if you lack adaptive it may never be knocked out - just limited for a loooong time if not indefinitely they must work together

Question 27

how does septic shock start?

Answer 27

massive TNF release leads to T cell overreaction.