Immunology

Question 1

Endotoxin binds to what?

Answer 1

Lipopolysaccharide -> binds to LPS- bind protein (found in plasma) -> binds to CD14 on macrophages -> triggers TLR4

Question 2

Peptidoglycan cell wall binds to what?

Answer 2

NOD receptors (intracellular) aka nucleotide- binding oligomerization domains-> cytokine expression

Question 3

Mannose is what? and binds to what?

Answer 3

Polysaccharide on bacteria and yeast -> mannose-binding lectin (MBL) from liver -> activates lectin pathway of complement activation

Question 4

What are pattern recognition components that activate an innate immune response?

Answer 4

-lipoteichoic acid on gram positive bacteria, double stranded RNA, unmethylated DNA, mannose, peptidoglycan cell wall, endotoxin

Question 5

What are the key surface receptors on macrophages?

Answer 5

CD14, Fc receptor, C3b receptor

T cell molecules: MHC II, B7, CD40

Question 6

What does CD14, Fc receptor and C3b receptor bind to?

Answer 6

CD14-LPS (gram negative)
Fc receptor- binds to Fc (antibodies)
C3b receptor- C3b (complement)

Question 7

What does B cell molecules receptor bind to: MHCII, B7, CD40?

Answer 7

MHCII- CD4
B7-CD28
CD40-CD40L

Question 8

What cytokines are produced by macrophages?

Answer 8

IL-1 and TNF-alpha

-IL-6, IL-8, IL-12

Question 9

What does IL-1 do?

Answer 9

• Increases synthesis of endothelial adhesion molecules-> allows neutrophils to enter inflamed tissue
• Endogenous pyrogen-> causes fever
• Acts on hypothalamus

Question 10

What does TNF-alpha do?

Answer 10

-Increases synthesis of endothelial adhesion molecules-> allows neutrophils to enter inflamed tissue
- Vascular leak-> septic shock if severe
-“cachectin: inhibits lipoprotein lipase in fat tissue
Reduces utilization of fatty acids -> cachexia

Question 11

What does IL-6 do?

Answer 11

Fever

Stimulates acute phase proteins production in liver

Question 12

What does IL-8 do?

Answer 12

Attracts neutrophils

Question 13

What does IL-12 do?

Answer 13

Promotes Th1 development (cell mediated response)

Question 14

What are the opsonins?

Answer 14

Attracters of neutrophils- IL-8, C5a, and IgG

Question 15

What surface markers do natural killer cells present with?

Answer 15

CD16- binds Fc of IgG

CD56- NCAM-useful marker for presence of NK cells

Question 16

What cytokines do Th1 cells secrete?

Answer 16

-IL-2, IFN-gamma

Question 17

What does IL-2 do?

Answer 17

• mostly from Th1 cells
• T-cell growth factor
• stimulates growth of CD4, CD8 T cells
• Also activates B cells and NK cells

Question 18

What does IFN-gamma do?

Answer 18

• since it’s secreted by Th1 cells -> activate even more Th1 cells and suppresses Th2 cells
• Activates macrophages (phagocytosis/killing)
• More MHC class I and II receptor expression from the APC (II) and all other cells (I)

Question 19

What are the Th2 cytokines?

Answer 19

IL-4, IL-5, and IL-10

Question 20

What does IL-4 do?

Answer 20

• Activates Th2 cells/suppresses Th1 production

- Promotes IgE production (parasites)

Question 21

What does IL-5 do?

Answer 21

• Activates eosinophils (helminth infections)

- Promotes IgA production (GI bacteria)

Question 22

what does IL-10 do?

Answer 22

• Inhibits Th1 production
• “Anti-inflammatory” cytokine only
• No pro-inflammatory effect

Question 23

Why is Th1 important?

Answer 23

Important for many intracellular infections

-works against infections that antibodies are not effective against

Question 24

How are giant cells formed from?

Answer 24

Formed from macrophages

Question 25

Mechanism of granuloma production

Answer 25

Th1 cells secrete IFN-gamma -> activates macrophages -> macrophages secrete TNF-alpha -> promotes granuloma

Question 26

What is IL-12 receptor deficiency?

Answer 26

- IL-12 cannot trigger differentiation T-cells into Th1 cells - No Th1 cells to produce IFN-gamma - Increased susceptibility to intracellular infections -> mycobacterial infections, disseminated salmonella, disseminated bacillus calmette- guerin (BCG) after vaccine

Question 27

MHC Class I

Answer 27

Binds TCR and CD8 | -One "heavy chain" plus beta-microglobulin

Question 28

What ligand does CD8 T-cells produce to induce apoptosis?

Answer 28

Produce Fas ligand-> binds to Fas (CD95) on surface of cells - activation caspases in cytosol-> cellular breakdown -> cell death with no significant inflammation (apoptosis) - "extrinsic pathway" of apoptosis

Question 29

What surface markers do Regulatory T cells express?

Answer 29

All express CD25 (classical marker) - also have CD3/4 - Produce anti-inflammatory cytokines -> IL-10 and TGF-beta - suppresses CD4/CD8 T cells

Question 30

How does a superantigen work?

Answer 30

Directly links MHC with T cell receptors -> to illicit response without being processed by APC - release a huge amount of cytokines -> IFN-gamma and IL-2 from Th1 cells - massive vasodilation and shock

Question 31

What are the 2 superantigens?

Answer 31

``` Staph aureus- toxic shock syndrome toxin (TSST-1) Strep pyogenes (group A strep) -> pyrogenic exotoxin A or C ```

Question 32

What type of cells do polysaccharide capsules bind to?

Answer 32

Polysaccharide capsules of many bacteria can stimulate B-cells but not T cells

Question 33

How are B cells activated?

Answer 33

1. ) T- cell dependent (protein) | 2. ) T-cell independent (non-protein)

Question 34

For T-cell dependent activation of B cells what 2 signals are required?

Answer 34

1. ) Cross-linking of receptors bound to antigen | 2. ) T cell binding (T-cell dependent activation)

Question 35

What is the mechanism for T cell dependent activation?

Answer 35

B cell can present antigen to T- cells via MHC class II-> Binds MHC class II w/antigen to TCR - Other T cell to B cell interactions need to occur 1. ) CD40 (B cells) to CD40 ligand (T cell) -> required for class switching 2. ) B7 ( B cells) to CD28 (T cell) -> required for stimulation of T-cell cytokine production

Question 36

Mechanism for T cell independent activation

Answer 36

Pathogens with many repeating subunits -> bind to multiple B cell receptors -> cluster so many B cell receptors together

Question 37

What are the key points of T cell independent antigen?

Answer 37

1. ) Very important for non-protein antigens -> polysaccharide capsules of bacteria and LPS 2. ) Weaker response, mostly IgM, no memory

Question 38

What are the 3 conjugated vaccines?

Answer 38

All have a non-protein polysaccharide capsule-> peptide antigen - H.influenza type B (Hib) - Neisseria meningitidis - Streptococcus pneumoniae

Question 39

What are the B cell surface proteins?

Answer 39

``` Proteins for binding with T cells 1.) CD40 (binding with T-cell CD40L) 2.) MHC Class II 3.) B7 (binds with CD28 on T cells) Other surface markers- all close to 20 1.) CD19: All B cells 2.) CD20: Most B cells, not plasma cells 3.) CD21 (complement, EBV) ```

Question 40

What are the triggers of class switching?

Answer 40

1. ) Cytokines (IL-4, IL-5 in Th2 response) | 2. ) T-cell binding (CD40-CD40L)

Question 41

Features of IgM

Answer 41

- 1st antibody secreted during infection - activates complement-> can activate complement and use c3b as opsonin - Prevents attachment of pathogens - cannot cross the placenta

Question 42

Features of IgG

Answer 42

- Major antibody of secondary response - **only antibody that crosses the placenta-> most abundant antibody in newborns - excellent opsonin- IgG1 and IgG3 are best opsonins - longest lived of all antibody types (weeks) - ** very important for encapsulated bacteria -> b/c it can coat encapsulated bacteria

Question 43

Features of IgA

Answer 43

- mucosal surfaces and mucosal secretions - crosses epithelial cells by transcytosis - excellent at coating mucosal pathogens-> so they cannot invade -> pathogens sweapt away with mucosal secretions - secreted into milk to protect baby's GI tract

Question 44

What pathogens contain IgA protease?

Answer 44

-S.pneumonia, H. influenza, Neisseria (gonorrheae and meningitidis)

Question 45

Features of IgE

Answer 45

- binds to mast cells and eosinophils - designed for defense against parasites - Mediates allergic reaction: seasonal allergies and anaphylactic shock

Question 46

B cell development timeline

Answer 46

``` Bone marrow/pre-infection: B cell undergoes VDJ rearrangement Lymph nodes/during infections: class switching for more specific response -> somatic hypermutation- stronger antigen binding over time -> Post infection: Memory B cell ```