Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Immunology I > Basics, innate receptors and complement > Flashcards

Basics, innate receptors and complement Flashcards

1
Q

E - Define innate immune system.

A
  • active at initial exposure to pathogen
  • immediate maximal response, rapid (min - h)
  • non-antigen specific
  • receptors are germline encoded
  • cells: macrophages, neutrophils, NK cells, DCs
  • no clonal expansion
  • no immunological memory
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

E - Define adaptive immune system.

A
  • response is antigen dependent and antigen specific and only after initial recognition of pathogen by innate immunity
  • there is lag-time between exposure and maximal response
  • receptors are specialized for each antigen (rearrangement of germline)
  • recognition of pathogen by ABs and TCRs
  • clonal expansion of T and B lymphocytes
  • creates immunological memory
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

E - Name the typical cells of innate immune system.

A 
macrophages
mast cells
NK cells
DCs
basophils, eosinophils, neutrophils
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

E - Name the typical receptors and molecules of the innate immune system.

A

Molecules: complement, antimicrobials (lysozyme, cathelicidin, ROS), type I IFNs, cytokines & chemokines

Receptors: PRRs and NKC receptors

  • TLRs
  • CLRs
  • NLRs
  • RIG-I like receptors
  • DNA sensors like ALRs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

E - What is the difference between humoral and cellular immunity?

A

Humoral: combats pathogens with antibodies (produced by B cells, can be transferred between individuals to provide passive immunization)

Cellular: primarily involves T cells which eradicate pathogens, clear infected self-cells and aid other cells in inducing immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

E - Define pathogen and immunopathology.

A

pathogen = microorganism that typically causes disease when it infects a host

immunopathology = detrimental effect of immune response on host cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

E - Compare properties of macrophages vs neutrophils.

A

Origin: macrophages differentiate from monocytes or are tissue-resident/neutrophils are granulocytes

Phagocytic: both highly

Present in: macrophages are found in all tissues (e.g. Kupffer cells in the ilver, microglia in brain, alveolar macrophages in lungs)/neutrophils are abundant in blood, but normally not present in healthy tissue; but neutrophils ARE the first to be recruited to the site of infection

Neutrophils are short lived (dead neutrophils are a major component of pus, form extracellular NETs to trap pathogens)/ macrophages are long lived.

Macrophages produce pro-inflammatory lipids and cytokines that recruit other immune cells (IL-1B, IL-6, CXCL8, IL-12, TNF-a).
Neutrophils recognize and phagocytose microbes, destroy microbes, release enzymes and antimicrobial peptides from granules.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

E - How are phagocytes activated?

A
  1. PRRs bind PAMP to activate the phagocyte
  2. Phagocyte ingests microbe and increases metabolic activity
  3. Activated phagocytes elevate antimicrobial activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

E - What is the role of TNF-a?

A

activates vascular endothelium
increases vascular permeability
-> enables entry of IgG, complement and immune cells to the site of infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

E - What happens during the inflammation upon infection?

A
  • bacteria trigger macrophages to release cytokines and chemokines
  • vasodilation and increased vascular permeability cause redness, heat and swelling
  • inflammatory cells migrate into the tissue, release inflammatory mediators (cause pain)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

E - Difference between thymus dependent and thymus independent antigen.

A

TD: require T cell help,
induce isotype switching and somatic hypermutation in germinal centers,
does not require repeating epitopes;
e.g. rhesus factor

TI: no T-cell help required for recognition by ABs (DCs can help via BAFF factor),
microbial Ag with repetitive epitopes,
limited isotype switching (stay IgM), no SHM
e.g. AB0 system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

E - Who was the first person to discover a vaccine and how?

A

Edward Jenner: observed that maids who cought cowpox had protection from smallpox

inoculation with cowpox protects the recipient agains smallpox

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

E - What are PAMPs and PRRs?

A

Pathogen Associated Molecular Patterns = molecules specifically associated with groups of pathogens that are recognized by cells of the innate immune system

Pattern Recognition Receptor = receptors of the innate immune system that recognize common molecular patterns on pathogen surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

E - Name different types of PRRs.

A 
Toll-like receptors
NOD-like receptors
C-type lectin receptors
RIG-I-like receptors
AIM2-like receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

E - Name TLRs in the endosome and their ligands.

A

TLR3: dsRNA
TLR7/8: ssRNA, viral RNA
TLR9: CpG DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

E - Dimerization of TLR leads to signaling in which IkB is degraded in the proteasome upon polyubiquitinilation. What follows?

A

NFkB becomes active, is transported in the nucleus where it acts as a TF and triggers cytokine genes expression.

17
Q

E - What are systemic effects of LPS?

A

Triggering inflammation all over the body.

18
Q

E - Name the 3 complement pathways.

A

Classical
Alternative
Lectin

19
Q

E - Explain the 2 ways of how complement activates C1s protease.

A

2 molecules of C1s (and 2 molecules of C1r) are bound to C1q

C1q binding -> C1r activation -> C1s cleavage and activation

C1q can bind either:

a) one pentameric IgM bound to bacterial surface in the staple form
b) 2 IgG molecules bound to bacterial surface nearby

ALSO: binding of cell surface directly by recognizing repetitive epitopes

20
Q

E - Describe how the complement is activated.

A

Classical pathway: C1q interacts with pathogen surface directly or ABs bound to it;
Lectin pathway: Mannose-binding lectin and ficolins recognize and bind carbohydrates on pathogen surface;
Alternative pathway: C3 undergoes spontaneous hydrolysis

All pathways then converge at the step of generating C3 convertase
C3 -> C3a (released) + C3b (bound to bacterial surface)
–> formation of C5 convertase
–> C5b binds C6 and C7; complex of those is bound by C8 (inserts into the membrane)
–> C9 bind this and polymerize to form a pore (membrane attack complex)

Also: byproducts ara anaphylatoxins (increase vascular permeability).

21
Q

Ž - Describe first immune system barriers of the skin.

A 
RNases and DNases
microcidal molecules (defensines, cathelicidins)
fatty acids
keratinized epithelium
commensal bacteria
22
Q

Ž - What is Janeway’s hypothesis?

A

to activate lymphocytes, you need to activate them by costimulatory signal, which is inducible by conserved microbial products that get recognized by germline encoded PRRs and NOT the antigen receptors themselves
that means that the actual detection of infection by the adaptive immune system and determining the origin of the Ag is under control of innate immune system

= explains why you need adjuvant addition to antigen to get immune responses in experiments

23
Q

Ž - What is C3 convertase made of in different complement pathways and how do you get C5 convertase from that?

A

classical and lectin pathway: C4b2a
alternative: C3bBb

to get C5: cleave C3 and add C3b to the complex

24
Q

Ž - Describe formation of MAC.

A

After C5 convertase cleaves C5:
C5b + C6 + C7 bind membrane
+ C8 to insert the complex in the membrane
+ C9(s) to actually form the pore

25
Q

Ž - What are anaphylatoxins and what do they do?

A

byproducts of complement activation (C3a, 4a, 5a)
increase vascular permeability = more cells + Abs + complement can come from blood to the site of infection
but if too much and systemically: anaphylactic shock
(generalized circulatory collapse, producing a shock-like response similar to systemic allergic reaction; life-threathening)

26
Q

Ž - Who discovered phagocytosis? Which cells of the immune system are capable of it?

A

Ilya Metchnikov

monocytes, macrophages
granulocytes (neutro, baso, eosinophils)
DCs
mast cells
B cells
27
Q

Ž - How are macrophages in different tissues called?

A 
liver = Kupffer cells
brain = microglia
lung = alveolar macrophages
28
Q

Ž - On which cells do you find C-type lectin receptors; which kinase is associated with them; what is the end result of signaling?
Name 3 specific CTLs.

A

on myeloid cells (especially macrophages, DCs)
Syk (except DC-SIGN), leading to formation of CBM complex after recognition of lectins (= carbohydrates on bacteria, viruses, fungi)
leading to proinflammatory cytokine production via NFkB/NFAT/MAPK-AP1

Dectin-1/2, mincle, DC-SIGN

29
Q

Ž - Name TLRs on plasma membrane. What do they recognize?

A

1+2: lipoproteins on bacteria (G+ and -)
2+6: lipoproteins on bacteria (G+ and -)
4+MD2: LPS
5: flaggelin

30
Q

Ž - Structure and signaling of TLRs?

A

leucine rich extracellular binding domain
intracellular TIR
- dimerization
- signaling via TRIF (3) or MyD88 (7/8, 9)
-> IRF3 -> type I interferons or
-> NFkB, AP-1 -> IL-1B, TNFa, IL-6

31
Q

Ž - How are endosomal TLRs activated (not the ligand)?

A

by lysosomal cysteine proteases cleaving their ectodomain

32
Q

Ž - French epidemiological survey discovered why some people get encephalitis upon HSV-1 infection, which is usually asymptomatic. What is it and why are these people sensitive to HSV-1 only and not allllll the viruses?

A

Mutation in TLR3 on fibroblasts = no signaling downstream

leukocytes do not only have TLR3, but other redundant pathways for sensing dsRNA viruses

33
Q

Ž - Which TLR is lacking in mice and which murine ones we don’t have?

A

no TLR8 in mice

they have additional TLR11-13

34
Q

Ž - What is used in lab to stimulate TLR3 and TLR9 response?

A

TLR3: poly(I:C)
TLR9: oligodeoxynucleotides with CpG motives

35
Q

Ž - On which cells are RLRs expressed?

A

non-hematopoietic: epithelial, endothelial, fibroblasts

+ cDCs

36
Q

Ž - How do RLRs distinguish between foreign and self RNAs?

A

foreign: 5’-triphosphate dsRNA, blunt-end base pairing at 5’ end
self: masked from detection by capping

37
Q

Ž - NLRs. Which complex is formed in signaling pathway via CARD domains interacting, what is the end result and in where does it play a role in health and disease?

A

nodosome -> NFkB and AUTOPHAGY

sensing and tolerance for commensal bacteria (secrete MDP)
immune responses against pathogenic bacteria
= destroyed homeostasis in Crohn’s disease

38
Q

Ž - Which cytokine is released upon ALRs signaling in macrophages? What triggers it?

A

DNA in cytosol

leads to IL-1B release

39
Q

Ž - Describe clonal selection theory. Who proposed it?

A

MacFarlane Burnet
theory to explain only ABs against the Ag you’ve been exposed to:

  1. a single progenitor -> rise to a large number of lymphocytes with different specificities = creating a repertoire
  2. self-reactive lymphocytes are removed by clonal deletion
  3. this creates a pool of mature naive lymphocytes that can recognize a foreighn antigen
  4. upon Ag recognition, lymphocyte is activated -> proliferation and differentiation = clonal expansion

Immunology I (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions