#11 Innate Immunity 01.29 Flashcards
what happens if you have neutropenia or NK deficiency?
you lack innate immunity and probs will die
name some examples of chemical components of innate immunity
fatty acids, lactic acid, sebum (skin) low pH/acidity (gut) enzymes, like pepsin and proteases (gut) salivary and tear enzymes, like lysozyme antibacterial peptides, like definsins
name a example of microbiological innate immunity
natural flora (skin and gut)
name some examples of mechanical components of innate immunity
epithelial cells joined by tight junctions (skin) longitudinal flow of air or fluid movement of mucus by cilia perspiration (skin) sloughing off of cells (skin)
what is a definsin?
human antimicrobial peptide
active against bacteria, fungi, many enveloped/unenveloped viruses
what aa is a definsin rich in?
arginine residues
what makes a definsin special?
- its ampiphatic character, which also puts + charge on hydrohillic side
- hydophillic residues create channel in bacterial membrane
what is the 2* structure of a definsin?
alpha helical
beta sheet
what make definsins?
neutrophils
macrophages
effector cells
what are the main source of definsins in the intestine?
paneth cells, which live in crypts of gut lumen and secrete definsins
what are two human antimicrobial peptides?
- definsins
2. cathelicidins
what is a cathelicin?
- 2* structure also alpha helical and beta sheet
- macrophages, neutrophils
- epithelial cells
when thinking about the complement cascade, you are always making what?
complements
what is the production of complements (cascade) a response to?
trick question!
nothing. NOT a response to infection, bc you are always making them
what by-product of the complement cascade is a recruiter for effector cells?
anaphlotoxins (the small bits)
generally describe the sequence of events for an infection in terms of innate and acquired response
- ubiquitous response of innate immunity
- induced response of innate immunity (amplified if early response overwhelmed)
- adaptive response
what pathway is part of the innate response and can most always take care of an infection?
the Alternative Pathway of complement activation
what do phagocytes recognize on bacteria/viruses?
pattern recognition receptors (PAMPS), aka general features of bacteria
do innate phagocytic responses to bacteria result in long lasting protective immunity?
no, they have the same response every time and it never improves
what are pattern recognition receptors (PRRs)?
host cell receptors that bind to common features of pathogens aka PAMPS
what are the initiators/mediators of neutophil rolling?
adhesion molecules
what acts as a “danger signal”?
PAMPs
what does PAMP recognition initiate?
phagocytosis
inflammatory cytokine production
expression of B7.1 and B7.2 on APCs
what are the 3 categories of PRRs?
- endocytotic PRRs
- signaling PRRs
- secreted PRRs
what are endoctotic PRRs?
promote phagocytosis of microorganisms by phagocytes without relaying an intracellular signal
what do endoctotic PRRs recognize?
carbohydrates
Ex: mannose, glucan, scavenger receptors
what are the two kinds of singaling PRRs?
- toll-like receptors (membrane)
2. NOD-like receptors (cytoplasm)
what are toll-like receptors?
- membrane bound**
- recognize microbial CONSTITUENTS
- mediate signaling that initiates cytokine production
what are NOD like receptors?
- cytoplasm**
- affinity for microbial PRODUCTS
- initiate signaling that results in production of inflammatory cytokines
toll-like receptors: gram + bacteria
TLR2:6 heterodimer
toll-like receptors: double stranded viral DNA
TLR3
toll-like receptors: gram - bacteria
TLR4:4 homodimer
toll-like receptors: flagellin
TLR5
toll-like receptors: single stranded viral RNAs
TLR7
TLR 8
toll-like receptors: bacteria and viruses
TLR 9
toll-like receptors: bacteria and parasites
TLR1:2 heterodimer
toll-like receptors: bateria
TLR1:2 heterodimer TLR2:6 heterodimer TLR4:4 homodimer TLR5 TLR9 (bac and virus)
toll-like receptors: viruses
TLR3
TLR7
TLR8
toll-like receptors: TLR10
who the fuck knows
what are secreted PRRs? examples?
PRRs secreted from host cells
Ex: c-reactive protein (CRP) and mannose binding protein
what complement cascade can mannose binding protein start?
Lectin Complement Cascade
what complement cascade can c-reactive protein (CRP) start?
Classical Complement Cascade
what is the order of binding in the CRP-indced classical complement cascade?
CRP binds phosphocholine
C1 binds to CRP
C1 : CRP :: C1 : ____
IgM pentameric or 2+ IgG
what cytokines are responsible for fever?
IL-6
IL-1-beta
TNF- alpha
what fever-inducing cytokine upregulates production of a co-pyrogenic cytokine?
IL-1-beta induces production of IL6
what cytokines activate vascular endothelium?
TNF-alpha
IL-1-beta
(this activating inflammation and movement of phagocytes into site of inflamm)
what cytokine activates NK cells? what do the NK cells produce?
IL-12
Nk cells produce IFN-gamma
what cell produces IL-6, IL-1-beta, TNF-alpha, IL-12?
macrophages
what coordinates innate response to microbial presence? how?
macrophages
by releasing cytokines
who produces acute phase response proteins?
liver
what induces the liver to produce actute phase proteins?
IL-6 especially
IL-1, TNF-alpha too
what are the 2 prominent acute phase proteins?
CRP
mannose-binding lectin
effects of IL-1, IL-6, TNF-beta
- liver producing acute phase proteins –> activation of complement opsonization
- neutrophil mobilization in bone marrow and endothelium –> phagocytosis
- increased body temperature via hypothalamus –> decreased viral and bac replication
- use protein and energy to generate increased body temp in muscle and fat —> “
4.
adaptive immune response is more efficient at ___ temperature
higher/elevated
what is acute phase response?
innate immune response that occurs soon after initiation of infection that involves the synth of acute phase proteins by the liver, which are secreted into the blood
what do acute phase proteins do?
amplify innate immune responses
CRP and MBP
what is an important feature od acute phase response?
induction of fever
CRP is structurally similar to ___ and :: can bind to phophocholine on bacteria
C1q
TNF-alpha does what? when can this be bad?
- contracts capillaries to restrict distribution of infection
- in sepsis, when it is systemically produced, it can shut down organ function
what are B1 B cells?
- B cells that are innate
- ## no clonal expansion or affinity maturation
what do B1 B cells respond to? what do they do when activated?
- they are cross linked by T independent type 2 antigens (TI-2), which semi-activates them
- they produce IgM and a little IgG
what Ab do activated B1 B cells produce?
IgM and a little IgG
is there class switching in B1 B cells?
yes, just a little to IgG
what do B1 B cells recognize?
repeating carbohydrate markers
how old is the host when B1 B cell innate response is finally developed?
5 YO
this means that those < 5 are more susceptible to encapsulated infections
what do virus infected cells produce?
type 1 interferons
IFN- alpha
IFN-beta
what do type 1 interferons do in innate immunity?
- they are produced by cells that are virally infected
- help to make adjacent cells less susceptible to infection
- upregulate MHC I
- activate NK cells
what is the role of NK cells in the innate immune response?
they “buy time” by killing infected cells to limit viral replication whilst acquired immune system has time to develop response
what do NK cells produce?
inflammatory cytokines that promote development of Th1 type response wh
name two processes that activate NK cells in acquired immunity response
type-1 interferons:
IFN-alpha
IFN-beta
macrophage cytokine release:
IL-12
what cells produce IFN-gamma?
innate:
NK cells
NK T cells
acquired:
Helper T cell/CD4
CTL T cell/ CD8
NK cells detect the imbalance of inhibitory and activating _____ on _____ cells via what kinds of receptors?
- ligands
- host
- Ig-like receptors
lectin-like receptors
NK response is innate or acquired?
innate
NK cells are programmed to kill any cell without ____
MHC I
can an NK cell ever clear an infection? what can? why?
- no
- CTLs
- CTLs recognize early viral replication :: few infected cells, whereas NK cells only recognize late viral replication and spread the contents when it kills cell
CTLs kill cells with ____
MHC I
MIC proteins are
stress proteins produced late in infection
dont present antigen
will an NK cell kill a host cell expressing MIC? is there an exception to this rule?
- yes
- yes, if there is enough MHC I to “hide” the MIC the NKC cell will pass over
(think of MHC I covering the MIC like the lambs blood keeping the baby boys safe from the shadow of death)