#11 Innate Immunity 01.29 Flashcards by Liza Lane

what happens if you have neutropenia or NK deficiency?

you lack innate immunity and probs will die

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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

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name a example of microbiological innate immunity

natural flora (skin and gut)

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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)

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what is a definsin?

human antimicrobial peptide

active against bacteria, fungi, many enveloped/unenveloped viruses

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what aa is a definsin rich in?

arginine residues

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what makes a definsin special?

its ampiphatic character, which also puts + charge on hydrohillic side
hydophillic residues create channel in bacterial membrane

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what is the 2* structure of a definsin?

alpha helical

beta sheet

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what make definsins?

neutrophils
macrophages
effector cells

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what are the main source of definsins in the intestine?

paneth cells, which live in crypts of gut lumen and secrete definsins

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what are two human antimicrobial peptides?

definsins

2. cathelicidins

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what is a cathelicin?

2* structure also alpha helical and beta sheet
macrophages, neutrophils
epithelial cells

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when thinking about the complement cascade, you are always making what?

complements

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what is the production of complements (cascade) a response to?

trick question!

nothing. NOT a response to infection, bc you are always making them

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what by-product of the complement cascade is a recruiter for effector cells?

anaphlotoxins (the small bits)

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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

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what pathway is part of the innate response and can most always take care of an infection?

the Alternative Pathway of complement activation

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what do phagocytes recognize on bacteria/viruses?

pattern recognition receptors (PAMPS), aka general features of bacteria

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do innate phagocytic responses to bacteria result in long lasting protective immunity?

no, they have the same response every time and it never improves

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what are pattern recognition receptors (PRRs)?

host cell receptors that bind to common features of pathogens aka PAMPS

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what are the initiators/mediators of neutophil rolling?

adhesion molecules

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what acts as a “danger signal”?

PAMPs

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what does PAMP recognition initiate?

phagocytosis
inflammatory cytokine production
expression of B7.1 and B7.2 on APCs

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what are the 3 categories of PRRs?

endocytotic PRRs
signaling PRRs
secreted PRRs

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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?

1. 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

1. liver producing acute phase proteins --> activation of complement opsonization 2. neutrophil mobilization in bone marrow and endothelium --> phagocytosis 3. increased body temperature via hypothalamus --> decreased viral and bac replication 4. 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)

#11 Innate Immunity 01.29 Flashcards

(79 cards)