Innate Immunity Flashcards Preview

Fundamentals Of Immunology > Innate Immunity > Flashcards

Flashcards in Innate Immunity Deck (63):

What does the innate response recognize?

PAMPs = Pathogen Associated Molecular Patterns

Recognizes common features of microorganisms (PAMPs) and the. Attacks, ingests and destroys directly


Which WBCs are part of the innate response?

All except most lymphocytes are part of innate response


What does the innate response do?

Ingest and destroy pathogens

Direct destruction

Communication link with adaptive response


What are the 8 components of innate immunity?

1) cells of the immune response
2) first line anatomical barriers (mucus membrane and skin)
3) antimicrobial substances
4) normal flora
5) sensor systems
6) phagocytosis
7) inflammation
8) fever


What are the granulocytes and what are their jobs?

Innate immune cells that contain granules
1) neutrophils: phagocyte and most abundant in innate response, only found in blood and bones (not tissue)
2) basophils, eosinophils, mast cells: important in expelling parasitic worms, active in allergic reactions


Which cell is a Granulocyte and a professional phagocyte? Where is it found?

Which cells are important in expelling parasitic worms and are active in allergic reactions?

Neutrophil, found only in blood and bones, never tissue

Basophils, eosinophils, mast cells (all granulocytes)


What are mononuclear phagocytes?

Monocytes and macrophages (which are derived from monocytes)

Monocytes circulate in blood

Macrophages are present in most tissues


What are macrophages, where are they particularly abundant, what are they called in different areas of the body?

Mononuclear phagocytes derived from monocytes.

Abundant in liver, spleen, lymph nodes, lungs, and peritoneal cavity

microglia =CNS
Kupffer cell=liver
Alveolar macrophages = lung
Osteoclasts =bone


What are dendritic cells and why are they important?

They are branching cells involved in antigen presentation to the adaptive response

They are the most important Antigen presenting cell


To which immune response do Natural Killer cells belong?

What is their job?

Innate response

They recognize and destroy host cells with no MHC Class I surface molecules

No antigen specificity, they augment adaptive response, they enable killing of infected host cells (self cells) with foreign protein in membrane


Explain the skin as the first line of defense

Most difficult barrier to penetrate

Perspiration: salt inhibits pathogen growth, locally produced antimicrobial substances kill microbes

Sebum secreted by sebaceous glands: keeps skin pliable, lowers skin pH (inhibitory to many bacteria)


Explain the mucous membrane barrier

Mucus helps wash surfaces
Propelling mechanisms to expel microorganisms and viruses out (such as mucociliary escalator of the throat)


Name the names and functions of the four antimicrobial substances utilized by skin and mucous membranes.

1) lysozyme: degrade peptidoglycan (tears, saliva, blood, phagocytes)
2) peroxidase: breaks down hydrogen peroxide to produce reactive oxygen (phagocytes, body tissues, saliva)
3) lactoferrin: sequesters iron from microorganisms
4) defensins: antimicrobial peptides inserted into microbial membrane


How does the normal flora contribute to innate defense?

Protects through competitive exclusion (not technically prt of IS) by covering binding sites so pathogens can't bind and competing for nutrients so they are unavailable for pathogens


What are the main points to remember about triggering an immune response?

1) IS is trained to not recognize our own antigens (self-recognition)
2) any antigen not self = foreign and can potentially trigger immune response (good vs. bad vs. neutral)
3) job of IS is to clear foreign antigen AND its source (whatever generated antigen must be eliminated)


What happens when the first line of barriers is breached? (First line is skin and mucous membranes)

1)recognition by tissue macrophages and complement
2) macrophage cytokines production (tissue cell sentries)
3) other cells produce cytokines, Epi cells express E and P selectins and ICAMS
4) cell migration and inflammation
5) activation of adaptive response


What do the epithelial cells' E and P selectins and ICAMs bind to?

E and P selectins bind sulfated-sialyl-Lewis

ICAMs bind integrins


What happens after a receptor binds to its ligand ?

Signal transduction, which leads to altered cell activity (activate/secrete/kill/etc)


What are PAMPs?

Pathogen associated molecular patterns


What is innate immunity's specificity?

Innate system recognizes structures that are shared by classes of microbes, such as PAMPs or damaged cells (damage-associated-molecular patterns)

Cannot tell cells apart, only groups/types (gram+/-) all have same gene to recognize patterns, same complement of receptors (PAMPs)


What is lectin?

Any group of proteins that are not antibodies and do not originate in an immune system but bind specifically to carbohydrate-containing receptors on cell surfaces.


Inmate vs adaptive receptor distribution?

Innate receptors are nonclonal: identical receptors on all cells of same lineage

Adaptive receptors: clonal: clones of lymphocytes with distinct specificities express different receptors


Adaptive immunity specificity?

Specific for structural detail of microbial molecules (antigens) and they may recognize no microbial antigens. Different microbes have distinct antibody molecules


Receptors of the adaptive?

Are encoded by genes produced by somatic recombination of gene segments, much greater diversity


What are the innate receptors? (6)

1) mannose-binding lectin
2) macrophage mannose receptor
3) scavenger receptors
4) till-like receptors
5) NOD-like receptors
6) RIG-I-like helicases (RLH)


What does each innate receptor bind?
1) mannose-binding lectin
2) macrophage mannose receptor
3) scavenger receptors
4) till-like receptors
5) NOD-like receptors
6) RIG-I-like helicases (RLH)

1) mannose-binding lectin: sugar residues it's a collectin)
2) macrophage mannose receptor: sugar residues (a c-type lectin)
3) scavenger receptors: anionic polymers & acetylated low-density lipoproteins
4) toll-like receptors: membrane/vesicle associated microbial antigens
5) NOD-like receptors: intracellular sensors for microbial products
6) RIG-I-like helicases (RLH): sense cytoplasmic viral RNAs


What are the effects of triggering innate receptors?

INC phagocytosis
INC proinflammatory cytokine production
INC production of co-stimulators molecules


Which TLRs are intracellular and which are extracellular receptors?

Extracellular: 2,4,5
Intracellular: 3,9


What does TLR-2 bind?

2 binds peptidoglycan (bacterial cell wall) extracellular


What does TLR-4 bind?

4 binds lipopolysaccharide (LPS), extracellular, outer membrane component of all gram- bacteria


What does TLR-5 bind?

5 binds flagellin, extracellular, protein that makes up bacterial flagella


What does TLR-3 bind?

3 binds dsRNA, sensed as a virus b/c it is degraded when formed in our cells, intracellular


What does TLR-9 bind?

9 binds CpG DNA, differently modified DNA from ours, treated as viral DNA and as if cell is infected, intracellular


What can cause inflammatory conditions?

Certain receptors will trigger inflammasome, which is involved in human inflammatory conditions (auto and chronic)
It is a cascade that certain microbes can trigger, and problems with the cascade can cause inflammatory conditions


What is a classically activated macrophage (M1) effector function?

1) microbicidal actions: phagocytosis and killing of bacteria and fungi
2) inflammation


What is an alternatively activated macrophage (M2) effector function?

1) wound repair and fibrosis
2) anti-inflammatory effects (inhibits inflammatory actions of M1


What activates the macrophages?

T cells, can be good/bad. (Chronic infection conditions b/c wrong effector pathway has been activated)


In general, describe what happens once phagocytes are activated/how are they activated ?

If macrophage binds to target using receptor--> signal transduction--> t.f.'s in nucleus so cell changes activity--> eat things/phagocytose (other cells: cytokines, produce things, all to kill microbe infected with)

Bind receptor> alter gene transcription> alter activity (cytokines, killing compounds, increase how much they eat, other EFFECTOR FUNCTIONS)


What are phagocytes? Where do they reside?

Specialized cells that engulf and digest microbes and cellular debris

many reside in tissue, more can be recruited from bloodstream and bones


Briefly Describe the process of phagocytosis

1) microbes bind to phagocyte receptors
2) phagocyte membrane engulfs microbe (becomes phagosome)
3) phagosome fuses with lysosome> phagolysosome (activation of phagocyte here)
4) killing of microbe by ROS, NO, lysosomal enzymes


How do bacterial capsules affect phagocytosis?

Capsules make bacteria hard to eat because it prevents process from starting (like its slippery, macrophage can't grab on)


What do ROS do in the action of phagocytosis?

They damage DNA and membranes even if it's aerobic bacterium (overload of reactive oxygen)


What is a phagosome? Phagolysosome?

Phagosome is a membrane bound vesicle that contains the microbe

Phagolysosome is the phagosome fused with lysosome (now has proteases, acidic pH, can now degrade microbe)


What are some ways microbes can escape phagocytosis? How common?

Escape before fusion, avoid altogether (capsule is slippery), prevent fusion of phagosome and lysosome, withstand the process (particularly nasty pathogens)

Most bacteria can't bypass the process, only the worst of the worst find a way around it


What is the complement blood alarm system?

Blood based alarm system: proteins floating in blood, usually inactive, but protelytic cascade> amplify self once triggered
Collection of a large number of blood proteins
- mostly produced by liver
- several are proteases activated by protelytic cleavage
-activated 3 different ways
- all pathways converge at production of a specific molecule and production of same set of effector proteins


What are the three pathways to activate the complement system? What does each need to start?

Alternative- microbial surface
Classical- antibody
Lectin- lectin


Describe the classical pathway of the complement blood system.

1) antibody must bind to cell
2) C1= first protease (cleaves proteins in two)
3) C1 activates C4
4) C4 split into C4a and C4b
5) C1 cleaves C2--> C2a +C2b
6) C3 convertase (C4b2a) splits C3 into C3a+C3b (important part: where converges)
I) C3b (opsonin) binds to and coats surface, upregulates phagocytosis
II) Other half of C3 complexes: C5 convertase (C4b2a3b
III) C5 convertase cleaves C5 to C5a and C5b (last protein to split)
IV) C5b binds to surface, allows C6,7,8 to bind in sequence (to surface) and C9 forms a pore
V) this forms MAC=C5b6789 (membrane attack complex)


What is the difference between classical and lectin pathway?

1) lectin is needed to start cascade (instead of antibody)
2) any C1 is MASP instead (searing proteases)


What makes up MAC (membrane attack complex)
C3 convertase?
C5 convertase?
C3 convertase for alternative?

MAC is C5b-9
C3 convertase is C4b2a
C5 convertase is C4b2a3b
C3 convertase alternative is C3bBb


Which pathway will be activated first time infected?

Lectin or alternative b/c either need lectin or microbial surface, respectively (classical need the antibody)


What is the alternative pathway?

Bypasses everything before C3, only needs microbial cell surface to start
1) C3 binds--> C3a and C3b autocatalytically, stabilizes reaction via Factor B and D (scaffold)
2) when B cleaved--> Bb and Ba
3) Bb complexes with C3b (C3bBb) =C3 convertase for alternative pathway
4) C3 convertase is stable and starts to cleave C3 to make more


What is the classical sequence?



What are cytokines?

Signaling proteins, they bind to surface receptors and regulate cell function

Ligands, communication link


Name each cytokine class function:
1) chemokines
2) colony stimulating factors
3) interferons
4) interleukins
5) tumor necrosis factor

1) chemokines: chemotaxis (directed chemical movement), neutrophils and other cells follow concentration gradient of chemokines to the source of infection

2) colony stimulating factors: leukocyte multiplication and differentiation

3) interferons: control of viral infections and inflammatory response

4) interleukins: role in innate and adaptive, produced by leukocytes

5) tumor necrosis factor: kill tumor cells and initiates inflammation


What is the primary secretive of cytokines?

Primarily secreted by Macrophages as a part of the innate response


Describe cell migration and adhesion of a neutrophil

1) neutrophil follows chemokines, once binds a chemokine it switches adhesions (adhesions are like a specific velcro)
2) other side of the adhesion Velcro is on vascular endothelial cells
3) selectins are the first part of the Velcro
4) rolling adhesion
5) integrins (on neutrophil) bind to their ligands on the endothelial cell surface--> strong binding that stops cell
6) cell flattens and pushed through gaps in vascular endothelium
7) cell enters tissue where infection is


What are the four Cardinal signs of inflammation and what is the overall cause that leads to them?

1) heat
2) pain
3) redness
4) swelling
All due to increase in vascular permeability= increased blood flow


What initiates inflammation? What is it? What happens?

Microbial invasion or tissue damage.

It is the body's response to these things.

Initiation> cascade of events that leads to dilation of blood vessels> leakage of fluid from vessels and migrations of leukocytes and phagocytes


What are the outcomes of inflammation?

Intent is to limit damage and restore function

But: can cause tissue damage due to toxic products and enzymes released from phagocytic cells

If limited to injured area: not much damage
If inflammation in delicate systems (nervous): severe consequences (brain and spinal chord inflammation in confined place!)


Fever is a product of which IS? What does it indicate? What does it contribute to host defense?

Product of innate

One of strongest indicators of infection

Fever inhibits growth of pathogens by raising temp above maximum growth temp and speeding up other body defenses (immune cells work faster at higher temps)


What are the body's fever-inducing substances called? (Body's temp reg am enter responds to them) endogenous vs. exogenous?


Endogenous: from within, fever-inducing cytokines

Exogenous: from without, microbial products


Are there deficiencies in innate response?
Can microbes find their way around the innate response?

Yes and yes

Resisting phagocytosis, ROS's, complement activation, anti microbial peptide abtibiotics, etc.


What are the pro-inflammatory cytokines?