Immunology II - Mclean

Question 1

3 modes of cytokine action:

Answer 1

autocrine: act on same cell
paracrine: act on nearby cells
endocrine: hormonal, act systemically. distant.

Question 2

Pleiotropy:
Redundancy:
Synergy:
Antagonism:

cascade induction:

Answer 2

Pleiotropy: one cytokine acting on different cells, multiple effects
Redundancy: multiple cytokine , one effect
Synergy: working together for an effect
Antagonism: cytokine blocks effect

cascade induction: a cell producing a cytokine that can act in another cell that will release another cytokine.

Question 3

3 popular cytokines that macrophages secrete:

important question!

Answer 3

These are referred to as Inflammatory cytokines **

Macrophages: IL-1, IL-6, TNFa.
IL stands for interleukins

Know how to identify which ones are inflammatory cytokines ^^^

Question 4

TH1 and TH2 relationship:

Answer 4

they downregulate each other.

“if you have a viral or bacterial infection, you want to activate TH1 and then th1 is going to downregulate THII.” Worm : downregulate th1 and upregulate th2.

Question 5

TH1 cells: play important role in what
TH2 cells:

Answer 5

TH1: viral, bacterial infections (macrophages engulf)
TH2: worms, larger microorganisms (B cells produce antibodies, bind to surface of worm Fc region then binds to eosinophil)

Question 6

Which cell has the Fas receptor?

Answer 6

Fas receptor on target cell.
Fas ligand on Cytotoxic T cell (CD8), doing the killing.

ONE WITH RECEPTOR WILL DIE

Question 7

CD8 cytotoxic t cell kill mechanism:

Answer 7

orients LG (lytic granules) and release lytic granule to site of cell contact. Move onto next cell and go down line.

Question 8

CD8 T cells release:

Answer 8

cytotoxins
cytokine: Interferon-y.
- this inhibits viral replication, increases processing / presentation of viral antigens via MHC class I, activates macrophages

Question 9

requirements of b cell activation:

Answer 9

1.)crosslinking of BCR (b cell receptor): binding of epitopes close to each other.
2.)b - cell co-receptors
3.)When T-cell help is involved, must do CD40 receptor on B cell binds to costimulatory molecule CD40 ligand on T cell.

Question 10

Thymus-independent antigens:

Answer 10

TI antigens are usually bacterial surface molecules with highly repetitive epitopes that crosslink many BCRs.

LPS bind to other receptors on B cell too.
Note: the LPS is similar to the CD40 ligand in t-dependent antigens.

Question 11

problems with thymus-independent antigens:

Answer 11

no isotype switching
no somatic hypermutation
no memory b cell formation.

Question 12

Mitogens:

Answer 12

nonspecifically activate b / t cells. Binds to site other than b / t cell receptors.

IMPORTANT: POKEWEED MITOGEN: stimulates both B and T cells.

Question 13

superantigens:

causes of this:

Answer 13

antigens that bind simultaneously to CD4 TCR and MHC-II of APC in absence of a specific peptide antigen.

can cause massive T cell activation, due to this superantigen not having to bind to the specific groove to elicit a response. can interact with multiple TCRs. Thus Large cytokine release.

Example: Toxic Shock Syndrome.

Question 14

Isotype switching: how are the particular isotypes determined?

Answer 14

determined by the cytokines released by the helper t cell.

Question 15

Hyper-IgM syndrome:

Answer 15

absence of CD40 ligand on T cells. thus, cant isotype switch, thus, too much IgM cause no switching.

Question 16

which immunoglobulin has a strong affinity to mast cells, eosinophils, basophils?

Answer 16

IgE.

They are almost always coated with IgE even if not bound to antigen due to insanely high affinity.

Note: mast cells generally found underneath mucosa of skin.

Question 17

When does a mast cell become activated?

Answer 17

when antigens crosslink at least 2 IgE molecules on its surface. contents will then be released.

Question 18

anaphylaxis:

Answer 18

type 1 hypersensitivity reaction. a systemic life threatening allergic response.

difficulty breathing, drop in BP.

Question 19

where antibodies are abundant:

IgM, IgG, IgA, IgE

Answer 19

IgM and IgG: mainly in plasma
IgG and monomeric IgA: lymph nodes / spleen, extracellular spaces
Dimeric IgA: secondary lymphoid tissue underlying mucosal surfaces. in breast milk. AKA secretory IgA, polymeric IgA.
IgE: surface of skin, under mucosal surface.

Question 20

Which antibody can travel across placenta?

mechanisms for other antibodies?

TARGET QUESTIONS

Answer 20

IgG can go directly across placenta.

IgA through breast milk

Question 21

neutralizing antibodies:

Answer 21

High affinity IgG, IgA.

Question 22

example of artificial passive:

example of natural passive:

Answer 22

artificial passive: inject horse with toxin, horse generates antibodies, inject serum into person.
natural passive: IgG directly across placenta to fetus.

Question 23

Natural killer cell similar to what?

Answer 23

they are like cytotoxic t cells but act earlier. They are less specific. can target XYZ, but cytotoxic t cells target X or Y or Z.

they provide innate immunity against intracellular infections. cytokines can activate these NK cells.

Question 24

How NK cells target cells for destruction:

Answer 24

1.) Reduced levels of MHC class I expression. This ->

Activates receptor NKG2D. If cell is hiding from CD8 cytotoxic t cell by downregulation of MHC class I receptor, then the activating receptor will bind, causing NK cells to release contents still.
Conclusion: Cytotoxic T cell is inhibited, but NK cell is thus activated.

2.) Antibodies. NK normally part of innate immune response, but can work with the adaptive here. NK cells interact with Fc region of antibody on target cell, orients cytotoxic granules and releases them. this mechanism is called antibody-dependent cell-mediated cytotoxicity (ADCC).

Question 25

complement proteins are….. produced where….

Answer 25

they are soluble proteins produced by the liver. they are zymogens: inactive enzyme but become active when cleaved.

Question 26

Cleavage of C4:

IMPORTANT

Answer 26

1.) C4 cleaved -> C4a (small) + C4b (large)
2.) C4b has enzymatic activity. C4a has inflammation properties.

Question 27

complement mechanism end result:

Answer 27

drill hole inside microbe, can surround capsule, coating it and opsonizing it.

can do inflammation, phagocytosis and lysis.

Question 28

Complement cascade:

Classical pathway:

Answer 28

triggered by antibodies bound to surface of pathogen.

1.) antibody binds to surface
2.) complement binds to antibody
3.) C4 gets cleaved to C4a and C4b
4.) C4b attaches to pathogen
5.) C2 gets cleaved to C2b and C2a
6.) C2b attaches to C4b, C2a inflammation as well.
7.) C4b - C2a complex = C3 convertase.

dont memorize all steps, only c3 convertase

Question 29

Complement cascade:

Alternative pathway:

Answer 29

triggered directly (no antibodies) by components of bacterial cell surfaces.

1.) C3 cleaves to C3a and C3b spontaneously.
2.) complement (C3b) binds to surface directly.
3.) Factor B comes in
4.) Factor D cleaves off piece of B, giving Bb and Ba.
5.) Properdin binds and stabilizes C3b - Bb complex.
6.) C3b - Bb - Properdin complex = C3 convertase

dont memorize all steps, only c3 convertase

Question 30

Complement cascade:

Lectin-mediated pathway:

Answer 30

triggered by mannose binding proteins (sugar) that are bound to surface of pathogens.

1.) sugar binds to surface directly.
2.) same as classical pathway after this first step.

Question 31

AFter complement cascade pathway when C3 convertase is made, what happens next?

Answer 31

C3 convertase cleaves C3 -> C3a + C3b

c5 convertase made. cleaves C5 -> C5b + C5a.
Note: C5b is the first post in the hole. (MAC, membrane attack complex).
Then add C6,7,8, complete with a bunch of 9’s. This completes circle of MAC.

Note: Most important and abundant complement molecule is C3.

Question 32

anaphylatoxins:

order of potency **

Answer 32

C3a, C4a, C5a. these iduce anaphylaxis.

potency: C5a > C3a > C4a *** target question.

Question 33

Hypersensitivity Reactions:

Type I:

Answer 33

Binding of antigen to IgE, release of histamine

more immediate response

order of response: Mast cells, then basophils, then eosinophils.

AKA IgE-mediated hypersensitivity

Classic example: Asthma.

Question 34

Hypersensitivity Reactions:

Type II:

Answer 34

targeting antigens on surface of cell. IgG binds to epitopes, causes lysis of the cell.

AKA: IgG-mediated Cytotoxic hypersensitivity. (Death of cell)

Question 35

Hypersensitivity Reactions:

Type III:

Answer 35

Not on surface of cell. Immune complexes form, which is antibody antigen floating around. Complements come in, can lodge in blood vessel walls, cause inflammation. Immune complexes made of IgG + soluble antigen.

AKA: Immune complex-mediated hypersensitivity.

Question 36

Hypersensitivity Reactions:

Type IV:

Answer 36

No antibodies involved in type IV. ***** classic question. Caused by antigens presented by APC to t cells which results in production of cytokines, activation of phagocytes and inflammation.

caused by effector TH1 cells, macrophage activation.

more delayed response

AKA: Cell-mediated hypersensitivity., or Delayed-type hypersensitivity.

Question 37

Past question: What are leukotrienes synthesized from?

Answer 37

Arachidonic acid.

Question 38

IgE mediated allergic responses: fast responses vs late response:

Answer 38

fast: wheal and flare at site of injection. due to histamine
late: due to leukotrienes