Midterm I (Ben) Flashcards by Dustin O

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

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What are the four principles of the adaptive immune response?

Antigen Specificity
High Antigen Sensitivity
Memory
Clonal Selection

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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?

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What are the components of innate immunity?

(7 items)

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

MGMIICN

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Which antibody type dominates the primary immune response?

And secondary?

primary = IgM
secondary = IgG

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What are some pro-inflammatory cytokines?

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

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What are some anti-inflammatory cytokines ?

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

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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

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What are the 4 different classes of chemokines?

How do their structures look?

C, CC, CXC and CX3C

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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

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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)

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

(via what molecules?)

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

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

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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.

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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.

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

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

What are 3 neutrophile effector functions?

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

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

(and their distinguishing surface markers?)

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

What are the 2 categories of phagocytic receptors?

(one has two subtypes)

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Opsonic receptors
- Fc and complement receptors
Pattern Recognition Receptors (PRRs)

What are 4 categories of Fc receptors?

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Fc-gamma
Fc-epsilon
Poly-Ig
FcRn

What are the functions of Fc-gamma receptors?

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

What are the functions of Fc-epsilon receptors?

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

What are the functions of PolyIg receptors?

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binds polymeric IgA
plays role in mucosal epithelial transcytosis

What are the functions of FcRn receptors?

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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

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

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

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

**Chronic Granulomatous Disease** * deficiency of phagocyte NADPH oxidase (PHOX) * leads to _granuloma formation_, _skin infections_ and _gingivitis_

What is an example of an _activating_ NK cell receptor? And an _inhibitory_ one? (With its ligand?)

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

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_

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 Kinase****s** * **IkB** is P-ated and degrades * **NF-kB** is disinhibited + translocates to nucleus * _co-stimulator_ and _cytokine_ expression is upregulated (ex: pro-IL-1)

What are 5 types of membrane-bound PRRs?

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

How can TLR activation increase antigen presentation efficiency?

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

What are the _plasma membrane_ TLRs and their ligands?

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

What are the _endosomal_ TLRs and their ligands?

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

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

* Components: **ASC**, **NLR**, **Caspase-1** * Activates **IL-1B** and **IL-18**, inducing inflammation

Midterm I (Ben) Flashcards

(35 cards)