immunity to microbes part I Flashcards
infections caused by pathogenic extracelular bacteria have 2 principal mechanisms:
- ____ causes tissue destruction at the site of infection
- bacteria produce ____ which have diverse pathlogic effects
- inflammation
- toxins
bacterial toxins are divided into 2 categories:
- ____ which are components of bacterial cell walls
- ____ whiuch are excreted by the bacteria
- endotoxins
- exotoxins
primary infection (extracellular bacteria) activation of complement pathways:
- alternative pathway caused by ____
- lectin pathway caused by ____
- classical pathway caused by ____
- LPS
- MBP
- C-Reactive Protein
complement causes:
- C3a and C5a →
- mast cells release →
- C3b →
- activate mast cells
- histamine and proteases that enhance blood flow
- opsonize the pathogen
upon extracellular bacteria primary infection:
local immune cell srelease chemokines/cytokines that activates endothelial cells and attracts neutrophils, especially through cytokine ____
IL-8
bacteria is opsonzied by C3b, promotes phagocytosis and killing by ____ and ____
neutrophils and macrophages
bacteria can be phagocytosed by DCs and processed to Ags → presented on ____
DC engulf and internalize bacteria and are activated by ____
MHC II
PRRs (e.g. TLRs)
mature DCs enter local LNs via ____ lymphatics and move to ____ cell zone
lymphocytes enter LNs via ____
DCs activate T cells (via Ag presented on MHC II) and begin ____
afferent T-cell
HEV
proliferation
naive T cells become differentitated towards ____ and ____ according to the DC signals
Th1 and Th2
Th cells migrate to germinal centers and interact with Ag-activated B cells resulting in ____ ____ and ____ maturatin
(early infections are characterized by ____ )
class switching (IgM → IgG/IgA)
affinity
IgM (low affinity with high avidity)
IgM is a very potent ____ complement activator that generates C3b opsonin
classical
some extracellular pathogens can evade immune responses:
- variation of surface ____ is key to evading humoral immunity
- inhibition of ____
- resistance to ____
- eliminate reactive oxygen species via ____
- Ags
- complement
- phagocytosis
- catalase
in the resolutioin of an infection, bacterial debris is removed by local ____ and ____ , or by ____ as soluble immune complexes
macrophages and neutrophils
antibodies
____ and ____ can independently (w/o MBL and CRP) actviate complement by the ____ pathway
alternative
the classical pathway is activated when ____ binds to Ab attached to Ag, activating ____ and ____ which cleave ____ and ____
C1q
C1r and C1s
C4 and C2
the lectin pathway is activated when ____ encounters conserved pathogenic ____ motifs, activating the ____ and cleaving ____ and ____
MBL
carbohydrate
MASPs
C4 and C2
prevention of host bystander damage:
- factor I
- DAF, C4BP
- CD59
- inhibits assembly of C3 and C5 convertase → lack of inflammation and classical complement
- inhibit assembly of C3 convertase → inhibit classical (C4BP) and alternative pathway
- inhibit MAC assembly → inhibit lysis
meutrophils and macrophages use surface TLRs, mannose receptors, and scavenger receptors to recognize extracellular bacteria. they use Fc receptors and complement receptors to recgonize intact bacteria or bacteria opsonized with Abs and/or C3b
- TLRs activate ____ activities of phagocytes
- mannose and scavenger recptors promote ____ of the microbes
- Fc and complement receptors promote both ____ and ____ of the phagocytes
- mimcrobicidial
- phagocytosis
- phagocytosis and activation
- TLR1 and TLR2 recognize bacterial ____
- TLR4 detects ____
- TLR5 recgonizes ____
- lipoprotein
- LPS
- flagellin
these TLRs mediate NFkB activation which requires adaptor protein MyD88
humoral effector mechanisms for extracellular microbes
- toxin ____
- opsonization and ____
- ____ activation
- neutralization
- phagocytosis
- complement
cell-mediated immunity for extracellular microbes:
- protein Ag of extracellular bacteria activates ____ T cells
- Th17 recruit neutrophils and monocytes promoting ____
- Th1 releases IFN-gamma that activates ____
- Th2 assists with ____ responses
- CD4+ helper
- inflammation
- macrophages (resulting in phagocytosis and killing)
- antibody
principal injurious consequences of host responses to extracelular bacteria are ____ and ____ ____
inflammation and septic shock
septic shock:
characterized by:
circulatory collapse → drop in blood pressure
IV coagulation
early phase of septic shock:
- caused by cytokines produced by ____ causing a cytokine ____
- TNF-alpha upregulates iNOS , IL-18 → futher activation of ____
- macrophges storm
- macrophages
late phase of septic shock: systemic
- cytokines stimulate production of ____ ____ ____ from liver
- leading to ____ activation
- acute phase proteins
- complement
cytokine ____ is a global suppressor of macrophage function
IL-10
certain bacteria (superantigens) bind MHC II to ____ subunit of TCR without Ag present in peptide binding groove
cause unregulated release of cytokines → ____ shock
can lead to polyclonal ____ cell activation
beta
septic
T-cell
red flags for superantigens:
- staphylococcus
- S. aureus
- S. pyogenes
- common in food poisening
- toxic shock syndrome
- streptococcal Tss or acute rheumatic fever)
____ protrude through the capsular surface, enabling the adhesions to bind to host receptors yet keeping the bactyerial surface hidden
PILI
the major mechanism used by bacteria to evade humoral immunity is variation of surface ____
Ags
the innate immunity is mediated by phagocytes and NK cells interactions among which are mediated by ____ and ____. may control bacterial growth, but elimination of the bacteria requries adaptive immunity.
IL-12 and IFN-gamma
(IL-12 activates NK cells to release IFN-gamme to macrophages so they can kill ingested bacteria)
the adaptive immunity is cell-mediated immunity in which ____ cells activate phagocytes to eliminate the microbes
T-cells
M. Tuberculosis (an intracellular bacteria):
- this bacteria invades macrophages and prevents lysosome from fusing with ____ → no phagolyosome
- activates macrophages to produce ____ and activates T cells
- CD4 T cells release ____ which recurits more macrophages and kills intracellular bacteria
- CD8 respond to MHC I through cross-presentation and ____ the infected cells
- phagosome
- IL-12
- IFN-gamma
- kill
intracellular bacteria evasion mechanisms:
- inhibition of ____ formation
- inactivation of ____ and ____
- disruption of phagosome ____
- phagolysosome
- ROS and NOS
- membrane
role of Th1/Th2 cells in infection outcome:
- Th1 cells:
- Th2 cells:
- activate phagocytes to kill ingeted microbes (classical macrophage activation)
- which inhibit this classical pathway of macrophage activation (alternative macrophage activation)
