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.

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?

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?)

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)

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

What are 4 categories of Fc receptors?

Fc-gamma
Fc-epsilon
Poly-Ig
FcRn

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

What are the functions of Fc-epsilon receptors?

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

What are the functions of PolyIg receptors?

binds polymeric IgA
plays role in mucosal epithelial transcytosis

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

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