Lecture 3 Flashcards
immediate immunity is recognition by ___________
non-specific/broadly specific effector cells
_________ involves recruitment of effector cells
early induced innate response
innate immunity involves the ____ phases of the immune response
first two
_________ form specialized barriers that provide innate defenses
epithelial cells
How does the skin provide defense?
- Multiple layers that grow outwards and shed
- differentiated keratinocytes produce beta-defensins
Differentiated keratinocytes produce _______ in lamellar bodies that are secreted into _________
beta-defensins, extracellular space
the _____ in the lung help to push mucus along and flush out microbes
cilia
_____ cells in the intestines produce an antimicrobial protein _________
Paneth,
alpha-defensins
the ________ is the hybrid between innate and adaptive response
dendritic cell
virtually all pathogens have an _______ phase
extracellular
What protective immunity exists in interstitial spaces, blood, and lymph?
complement, phagocytosis, antibodies
Where do antimicrobial peptides and antibodies, especially IgA act?
epithelial surfaces (extracellular)
What protective immunity exists for pathogens in the cytoplasm?
NK cells and cytotoxic T cells
Activation of macrophages by _____ or _____ can induce macrophages to kill _____ without killing the host
NK cells, helper T cells, pathogens living within vesicles
IFN activates _____ response on _____
antiviral response, its own/nearby receptors
Which pathways does IFN act on?
PKR kinase, OAS synthetase, Mx proteins, ADAR, NOS
Viral mRNA translation is inhibited by ____
PKR kinase
OAS synthetase will ____ viral mRNA
degrade
The ADAR pathway will ____ viral mRNA
edit to deaminate adenosine to inosine
Mx proteins induce resistance to ___________
viral replication
_____ will increase MHC class I expression in all cells
IFN alpha and beta
Which cells does IFN activate?
macrophage, dendritic, NK
What are the direct mechanisms pathogens use to damage tissue?
exotoxin, endotoxin, direct cytopathic effect
What are examples of diseases that result from exotoxins?
tetanus, diptheria, tonsilitis, cholera, food poisoning
What is an example of a disease that results from endotoxin?
sepsis, plague, dysentery, typhoid fever, pneumonia, meningitis
What are examples of diseases with direct cytopathic effect?
chickenpox, small pox, polio, measles, influenza, cold sores
What are indirect mechanisms of tissue damage by pathogens?
immune complexes, anti-host antibody, cell-mediated immunity
immune complexes are activated by _______ and deposit in the _______
complement induced inflammation, kidney
In _______, antigens disguise themselves as similar to the host, and the large volume of antibody titers created may attack ____ cells. An example is _____.
anti-host antibody, host, rheumatic fever
In cell-mediated immunity, the pathogen will change molecule on cell surface so that it will be attacked by _____
NK cell
Which branch of the immune system can discriminate between closely related molecular structures?
innate and adaptive
TLR2:TLR6
diacyl lipopeptides
TLR1:TLR2
triacyl lipopeptides
TLR5
flagellin
TLR4
(plus MD-2) LPS
TLR3
dsRNA (intracellular)
TLR7
ssRNA (intracellular)
TLR8
ssRNA (intracellular)
TLR9
unmethylated CpG motif
How many TLR are there in humans?
10 but the function of TLR10 is unknown
Which TLRs are located intracellularly?
3, 7, 8, 9
5 important families of cytokines/chemokines produced by macrophages
IL-1beta, TNF-alpha, IL-6, CXCL8, IL-12
What are the local effects of IL-1beta?
activate vascular endothelium, activates lymphocytes, destruction of local tissues, increases access of effector cells
What are the systemic effects of IL-1beta?
fever, production of IL-6
Local effects of TNF-alpha
activates vascular endothelium, increases vascular permeability, leads to increased entry of IgG, complement, and cells to tissues and increased fluid drainage to lymph nodes
Systemic effects of TNF-alpha
fever, mobilization of metabolites, shock
Local effects of IL-6
lymphocyte activation, increased antibody production
Systemic effects of IL-6
fever, acute-phase protein production
Local effects of CXCL8
chemotactic factor recuits neutrophils, basophils, and T cells to the site of infection
Local effects of IL-12
activates NK cells, induces differentiation of CD4 T cells into TH1 cells
chemokines act on _____ receptors
G protein coupled
Selectins are proteins on activated endothelium that ______
bind carbohydrates, initiate leukocyte-endothelial interactions
Integrins are proteins on ______ that _______
leukocytes; bind to cell adhesion molecules and extracellular matrix. Strong adhesion
How does normal flora, local chemical factors, and phagocytes protect against infection?
prevents adherence to epithelium
What protections exist for local infections when the epithelium has been penetrated?
wound healing induced AMPs, complement system, phagocytes
_____ serves as a physical barrier to stop the spread of local infection
blood clotting
At what stage in infection do dendritic cells migrate to lymph nodes to initiate adaptive immunity?
During local infection of tissue
What are the four steps in cell migration from the blood to the tissue?
Rolling adhesion, tight binding, diapedesis, and migration
_____ make up the first wave of cells that cross the blood vessel wall to enter an inflamed tissue
neutrophils
_____-mediated adhesion is weak
selectin
P-selectin is induced by ______ and will bind to ________ on leukocytes to initiate rolling adhesion
B4, C5a, histamine, TNF-alpha, or LPS;
leukocyte sialyl LewisX
Leukocyte integrins ____ and _____ will tighten binding with _____ and _____ on endothelium
LFA-1, CR3, ICAM-1, ICAM-2
Diapedesis is mediated by ____, ____, ____, and ____
LFA-1, CR3, PECAM, and CD31
Chemokines _____ and _______ facilitate the fourth step of migration into tissue
CXCL8 and CCCL2
the _____ immune response results in inflammation
innate
______ are proteins that bind sugar residues. Ex: _____ and _____
Lectins; dectin-1 and mannose
Class A ________ recognize poylanionic sequences of many types
scavenger receptors
______ recognizes and internalizes lipids
CD36
Complement receptors internalize ________
complement-coated bacteria
What happens to internalized phagosomes?
fusion with lysosomes to form acidified phagolysosomes
Where does breakdown by acid hydrolases occur?
In phagolysosomes
_____ and _____ are GPR involved in respiratory burst
C5a and fMPL
____ induced assembly of NADPH oxidase
Rac2
Bacterial _____ activates Rac2
fMPL
NADPH oxidase aka ______, leads to a ______ with transient increase in oxygen consumption
phagocyte oxidase; respiratory burst
Antimicrobial mechanisms of phagocytes
acidification, toxic oxygen derived products, toxic nitrogen oxides, AMPs, enzymes, competitors
Cytokines produced by _____ cause _______ of the local blood vessels
macrophages; dilation
Leukocytes move to the ______ as a result of increased expression of adhesion molecules by the _______
periphery; endothelium
________ are dendritic cells of the skin
Langerhans cells
_____ engagement causes maturation of DC
TLR4 and CD14
Once DCs are fully active they become attracted to ______ in the _____
chemokines; lymph nodes
_____ and _____ are costimulatory molecules that are important in interacting with adaptive immune response
CD80 and CD86
Within lymph nodes DC upregulate ___, ____, and _____ expression
CD80, CD86, and MHC molecules
immature dendritic cells are resident in _______
tissue
Where do DCs mature?
Mature as they migrate through lymphatics
Mature _______ activate ______ T cells
DCs; naive
Lymph nodes exist at _______ lymphatics
converging
______ lymphatics drain fluid and carry antigen presenting cells
Afferent
Where are B cells located in lymph nodes?
follicles
Where are T cells located in lymph nodes
parafollicular region and paracortex
What occurs in germinal centers?
B cells undergo intense proliferation
