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Flashcards in Midterm I (Ben) Deck (35):
1

What is the difference between the size of peptide fragments bound by MHC-I vs. MHC-II ?

 

And the difference in how the peptide fragments fit into the MHC molecule?

  • MHC-I - binds 8-9 AA peptides w/out overhang
  • MHC-II - binds 11-20 AA peptides w/ overhang

2

What are the four principles of the adaptive immune response?

  1. Antigen Specificity
  2. High Antigen Sensitivity
  3. Memory
  4. Clonal Selection

3

How does a graph of the number of micro-organisms in an infected individual vs. time look...

for a normal person/someone lacking innate immunity/someone lacking adaptive immunity?

4

What are the components of innate immunity?

(7 items)

  • macrophages
  • granulocytes
  • mast cells
  • immature dendritic cells
  • innate lymphoid cells
  • complement
  • natural autoantibodies

MGMIICN

5

Which antibody type dominates the primary immune response?

And secondary?

  • primary = IgM
  • secondary = IgG

6

What are some pro-inflammatory cytokines?

  • IL-1 / 12 / 17 / 18 / 33
  • TNF
  • IFN-y

7

What are some anti-inflammatory cytokines ?

  • IL-10 / 13 / 35
  • IFN-alpha
  • TGF-beta

8

What is the general structure of most cytokine receptors?

What is one exception?

  • most are singe-pass receptors in dimer/trimer form
  • chemokine receptors are 7 TM domain Rs

9

What are the 4 different classes of chemokines?

How do their structures look?

C, CC, CXC and CX3C

10

What are two innate immunity-related molecules found in saliva?

(Where else are they found? What are their actions?)

  • Lactoperoxidase - also in mammary glands/milk, catalyzes H2O2 oxidation of acceptor molecules which then have bactericidal activity
  • Lysozyme - also in sweat/tear fluid, is an peptidoglycan N-acetylmuramyl hydrolase enzyme which cleaves bacterial cell wall components

11

What are the two types of recruited macrophages based on their activation pathway?

(How are they activated and what are their functions?)

  • M1 Macrophages - via IFN-y 
    • pro-inflammatory, anti-tumor, host defense
    • (also activated by GM-CSF or LPS)
  • M2 Macrophages - via IL-4 or IL-13
    • wound healing, angiogenesis, scavenging (suppress immune defenses)
    • (also via vit. D, PGE, cortisol, IL-10, M-CSF)

12

What are 3 types of signals sent to macrophages by apoptotic cells?

(via what molecules?)

  1. Find Me - via MCP-1 and IL-18
  2. Eat Me - via P-serine
  3. Tolerate Me - via IL-10, TGF-B and PGE-2

13

What is the first (of 3) stage of neutrophil extravasation and the molecules involved?

Rolling involves binding of neutrophil membrane PSGL-1 (P-selectin glycoprotein ligand) and endothelial P-selectin.

 

S-Lex (sialyl-Lewis X, a tetrasacch. carb attached to O-glycans on cell surfaces) may also bind E-selectin

14

What is the second (of 3) stage of neutrophil extravasation and the molecules involved?

Adhesion involves binding of neutrophil membrane integrin LFA-1 (lymphocyte function-associated antigen) to endothelial ICAM-1.

15

What is the third stage (of 3) in neutrophil extravasation and the molecules involved?

Diapedesis involves chemoattraction of neutrophils by CXCL8 (AKA IL-8) via their CXCL8-R.

16

Describe the process of "neutrophil swarm", including chemical messengers involved.

  1. Injury/infection induces LTB4 release in tissues, stimulating rapid neutrophil accumulation.
  2. C3XCL1 "fractalkine" then attracts C3XCR1+ macrophages to the site

17

What are 3 neutrophile effector functions?

  1. Phagocytosis - with intravesical killing of pathogens (both O2-dependent + indepedent) and lysosomal degradation
  2. Degranulation - "frustrated phagocytosis" involving release of cytotoxic enzymes
  3. NETosis - release of extracellular DNA traps

18

What are the 3 different categories of dendritic cells (one has two subcategories)? 

(and their distinguishing surface markers?)

 

  1. Myeloid (both are CD11c+)
    • Conventional DC1 - CD1c+ (40-50%)
    • Conventional DC2 - CD141+ (5-10%)
  2. Plasmocytoid (40-50%) - eccentric nucleus and high rER content
    • ​​CD123+ and CD11c+
  3. Monocyte-derived
    • ​​(CD14+, CD11b+)

19

What are the 2 categories of phagocytic receptors?

(one has two subtypes)

  1. Opsonic receptors
    • Fc and complement receptors
  2. Pattern Recognition Receptors (PRRs)

20

What are 4 categories of Fc receptors?

  1. Fc-gamma
  2. Fc-epsilon
  3. Poly-Ig
  4. FcRn

21

What are the functions of Fc-gamma receptors?

  • binds IgG
  • facilitates phagocytosis (Fc-gamma-R-I)
  • may suppress B cell function (Fc-gamma-R-IIb)
  • induces macrophage respiratory bursts

22

What are the functions of Fc-epsilon receptors?

  • binds IgE
  • high affinity form FcE-R-I on basophils + mast cells plays role in allergy

23

What are the functions of PolyIg receptors?

  • binds polymeric IgA
  • plays role in mucosal epithelial transcytosis

24

What are the functions of FcRn receptors?

  • In the placenta: binds maternal serum IgG to protect it from degradation during transfer of passive immunity from mother to fetus
  • On luminal side of neonatal gut epithelium: binds IgG from breast milk to protect it from acidic gut pH and aid its absorption

25

What are two oxygen-dependent methods of intravesical killing involving free radicals?

  • Peroxidase-independent - NADPH oxidase on phagosome membrane creates O2- which makes H2O2 etc. to kill microbes
  • Peroxidase-dependent - peroxidase enzymes make hypochlorite using H2O2, HClO- then kills microbes

26

Describe the NO Pathway of intravesical killing.

  • TNF and IFN-y stimulate iNOS activity, producing NO from O2 and L-Arg
  • NO is toxic to microbes

27

What disease is related to a deficiency affecting intravesical killing mechanisms?

Chronic Granulomatous Disease

  • deficiency of phagocyte NADPH oxidase (PHOX)
  • leads to granuloma formationskin infections and gingivitis

28

What is an example of an activating NK cell receptor?

And an inhibitory one? (With its ligand?)

  • NKG2D activates
  • NKG2A inhibits (binds MHC-I)

29

What are the 3 types of innate lymphoid cells?

What do they produce/do?

  • Type I: NK cells, make IFN-y
  • Type II: make Th2 cytokines (IL-4/5/9/13)
  • Type III: make IL-17/22

30

Give an example of a signalling pathway set off by a Toll-like receptor.

With TLR-4...

  • LPS binds LPS-binding protein (LPB) on receptor
  • IC MyD88 adaptor sets of Ser/Thr Kinases
  • IkB is P-ated and degrades
  • NF-kB is disinhibited + translocates to nucleus
  • co-stimulator and cytokine expression is upregulated (ex: pro-IL-1)

31

What are 5 types of membrane-bound PRRs?

  1. NK cell Rs
  2. Complement Rs
  3. Lectins 
  4. Scavenger Rs
  5. Toll-like Rs

32

How can TLR activation increase antigen presentation efficiency?

by upregulating expression of MHC and co-stimulatory molecule B7 expression

33

What are the plasma membrane TLRs and their ligands?

  • TLR1:TLR2 - lipopeptides
  • TLR2 - peptidoglycan
  • TLR4 - LPS
  • TLR5 - flagellin
  • TLR2:TLR6 - lipopeptides

34

What are the endosomal TLRs and their ligands?

  • TLR3 - dsRNA
  • TLR7 or TLR8 - ssRNA
  • TLR9 - CpG DNA

35

What are the components of inflammasomes and what do they activate?

  • Components: ASCNLRCaspase-1
  • Activates IL-1B and IL-18, inducing inflammation