Immunology Exam One Flashcards

1
Q

What is the difference between an antigen and an epitope?

A

An antigen can be anything, an epitope is the specific structures within an antigen which an antibody can recognize/bind

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2
Q

What cells have MHC I

A

All nucleated cells have MHC I because any cell can be infected

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3
Q

What cells have MHC II? What does it do?

A

All immune cells: Used to communicate with CD4 helper cells and alpha beta t-cell-receptors to communicate what was found. Presents processed antigen

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4
Q

What must generally happen to the antigen before presentation in MHC molecules?

A

The epitope is often buried, so the protein must be broken up. remember the hotdog in a bun.

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5
Q

IgA is found where and in how many imers?

A

It is in mucus and is dimeric

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6
Q

Which antibody is secreted first during an immune response and how many subunits does it have?

A

IgM is secreted first in the immune response and is the largest isotype as it is pentameric.

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7
Q

Which antibody can initiate complement with only one antibody?

A

IgM because it is so large, with many monomers. IgG needs two spaced near each other to initiate classical complement.

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8
Q

What is special about IgG

A

It is the most secreted antibody and is monomeric.

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9
Q

What two words describe the cell layer on top of blood following centrifugation (it looks white)

A

Its the plasma and buffy coat. Plasma has antibodies and complement proteins and the buffy coat is where the white blood cells are and is the coat on top of the red blood cells.

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10
Q

What are the innate lymphocytes and which are in the grey zone between adaptive and innate immunity?

A

Innate lymphoid cells (probably og starting point for later adaptive immune cell differentiation), Natural Killer cells, eosinophils, neutrophils, basophils, monocytes.

The grey zone cells: gamma delta T-cells and NK-T cells both recognize lipids

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11
Q

What are the adaptive immune cells

A

CD4 (alpha beta TCR) Th1-antiviral Th2-antibacterial/parasite Th17-antibacterial Treg-modulates immune response.
CD8 (alpha beta TCR)
B1 cells and B2B cells (B1 makes IgM only)

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12
Q

What are the central lymphoid organs?

A

Thymus where T-cells are educated

Bone marrow- where B-cells are educated

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13
Q

What is a Peyers patch and what does it do?

A

The Peyer’s patch is found in the intestine. They have special M cells which sample the lumen. They feed the samples to T and B cells located below. If shit goes awry IgA is secreted along with peptides like defensin in combo with gut microbio to attack pathogens.

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14
Q

What is the general components of zymogens and what must occur for them to become activated?

A

There is generally a pro-region attached to the amphipathic peptide responsible for activity. The pro-region dampens activity and must be cleaved away using a protease to activate the zymogen.

Amphipathic nature allows for association with the membrane and with one another to open pores in the membrane. Thus subverting selective permeability = DEATH

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15
Q

What are PAMPs?

A

Pathogen Associated Molecular Patterns
Thing PPG and its repeating NAG-NAM or the mannose residues of mycobacteria. They are general ie gram negatives generally have an LPS but this does not give large specificity on what organism this actually is.

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16
Q

What is the Lectin pathway in Complement?

A

Mannose binding lectin and ficolin bind to sugars on pathogens (PAMPS). They then recruit membrane associated serine proteases which cleave C4 and C2 into C4a, C4b and C2a and C2b which then goes on to the rest of the pathway normally.

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17
Q

What is the alternate pathway in complement

A

C3 can be hydrolysed spontaneously. Our cells have inhibitors of C3b so when it binds to us it does nothing. Bacteria lack this so when it binds it recruits factor B which alters conformations upon binding and is cleaved by factor D. This complex now is a C3 convertase and makes more C3b. The properdin just stabilizes the complex

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18
Q

What is the classical cascade in complement

A

C1qrs binds to antibody on the surface. This cleaves C2 and C4 making C2a, C2b and C4a, C4b. C2b and C4b bind the surface and associate together to make a C3 convertase. This breaks C3 into C3b which binds the C4bC2b complex and C3a (anaphylatoxin signals chemotaxis) C2bC4bC3b complex is a C5 convertase and cleave C5 into C5a and C5b. C5b binds and recruits C6,7,8 which then inserts C9 in a ring forming the MAC.

C3b= coat for opsonization
C3a and C5a= anaphylatoxin –> recruit immune cells via chemotaxis.

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19
Q

What are B1-b cells and where are they located?

A

They are located in the margins of the white and red pulp in the spleen
They make IgM and never switch

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20
Q

What are innate leukocytes

A
Neutrophils, basophils and eosinophils
Monocytes
Natrual killer lymphocytes
Gamma delta t-cells (lipids)
invariant NK T-cells
B-1 marginal zone B-cells --> macrophage like make IgM (natural antibody)
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21
Q

What is the function of Gamma Delta T-cells?

A

They farm epithelium, because they kill cancerous/ infected cells. They recognize self and lipids. And represent most of the lymphocytes within the epithelium.

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22
Q

How are tissues seeded by gamma delta T-cells?

A

As the fetus develops different variable regions become activated. It seems this is somehow directing gamma delta t-cell seeding in early fetal development.

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23
Q

What are toll-like receptors?

A

They are PRRs or pattern recognition receptors especially important in the detection of PAMPs. They induce the expression of host defense mechanisms. When Toll was knocked out in fruit flies they became extremely susceptible to fungal infection. Homologs were found in humans and thus called Toll-like

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24
Q

How many TLRs are there in humans and what is their specificity

A

There are 10 TLR genes in humans and they have very wide specificity. LPS, flagellin, CpG DNA, dsDNA, ssRNA ect.

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25
Q

Where are TLRs found?

A

They are expressed in stromal cells, certain epithelial cells, DC, macrophages and B cells thus allowing a variety of tissues to mount antimicrobial responses.

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26
Q

How do TLRs bind their ligand

A

They generally come together as dimers and can be homotropic or heterotropic. This probably lends to a larger diversity of pattern recognition than with homotropic dimers alone would allow.

27
Q

What do TLRs do

A

They oligeramize so that their tails come together and initiate signaling cascades via kinase activity leading to the activation of transcription factors which then activate proinflammatory genes

28
Q

Cytoplasmic PAMP example

A

RIG-1 and MDA 5 grab onto viral mRNA and form a complex with TRIM25 then a bunch of these oligeramize on the mitochondrion. This activates kinase cascades which activates IRF-3 and destroys NFkappaB inhibitor IkappaB both IRF-3 and NFkB now activate proinflammatory genes

29
Q

What are IRFs

A

Interferon response factors they are the bits that bind the promoter regions of pro inflammatory genes and activate interferon genes.

30
Q

Describe what happens with when a cell is infected with an intracellular pathogen (interferon feedback loop)

A

A cell uses PAMP (toll-like) receptors both inside and out to detect the pathogen. This leads to kinase cascades which activates transcription factors (also called interferon stimulated response elements [ISRE] and Interferon response elements [IRFs]) Which bind to the promoter of the genes and produce either interferon or anti pathogen proteins (antiviral, microbial ect).

The interferons are released and warn nearby cells
They bind interferon receptors –> kinase cascade –> IRFs and ISRE –> interferon and defense peptides and warn other cells. Making one large feed back loop.

31
Q

What are two examples of interferons

A

IRF and NFkB activate OAS1 which is a protein that becomes a tetramer that recognizes viral mRNA (triphosphate cap). When it does it activates and becomes an RNAse and cleaves, non-specifically, dsRNA to prevent viral replication.

MxA is activated by IRF and NfkB and makes a protein that oligermizes and can recognize the geometric shape of viral protein coats. It then coats the protein and traps it so it cannot replicate and waits to be killed by a NK cell.

32
Q

What interferons are expressed by all cells?

A

Type I and II alpha beta gamma

33
Q

What interferons are expressed by immune cells only?

A

Type II IFN-gamma

34
Q

What cytokines/chemokines are expressed in a viral response?

A

Interleukin-12 (IL-12) and interferons (IFN) they activate CD8+ T-cells and mark themselves for death

35
Q

What chemokine/cytokines are involved in antibacterial/parasite/yeast response?

A

Interleukin-17 IL-17 Activates endothelial cells makes them sticky and increases CXCL8 + attracts neutrophils

36
Q

What is the proinflammatory triad? What do they do? When are they expressed?

A

Interleukin 1beta, TNF-alpha, and IL-6
they have two functions- they have local effects like IL-12 and IL-17 but they also have systemic effects and induce fever. They are expressed during nearly any infection.

37
Q

What does CXCL-8 do?

A

They are a chemotactic factor it attracts neutrophils and macrophages and whatnot to the site of infection. It is also a chemical that sticks onto epithelial cells and activates cells as they roll on by. Signals that the passing leukocyte needs to complete extravasation via diapedesis.

38
Q

How does extravasation occur?

A

A WBC is rolling along the glycocalyx and then a chemokine receptor recognizes CXCL8. This in turn activates integrins which grab onto ICAM-1 with firm adhesion. The WBC then uses this to roll along the epithelial cell until it comes to a cell junction. It then signals at that junction to PECAM 1 that its squeezing through.

39
Q

What are the steps in phagocytosis?

A
  1. binding of pathogen through receptors: sugars, FC region, lipids ect.
  2. engulfment
  3. digestion-fusion of lysosome with endosome.
  4. PAMP receptors recognize what was destroyed –> antigen presentation –> offense like degranulation or chemokine production.
40
Q

What are NETS

A

neutrophil extracellular traps, literal nets made of chromosomal DNA

41
Q

Systemic sepsis or septic shock cause

A

macrophages in the liver see LPS this is recognized by PAMP receptors leading to a shit ton of TNF-alpha production. This is distributed throughout the body, this causes edema or WBC leaving the blood and going into tissues because they are all alerted –> vessel collapse –> intravascular coagulation leading to death.

42
Q

What is a monoclonal antibody?

A

Antibodies which come from a single B-cell clone and which recognize only a single epitope.

43
Q

What is a polyclonal antibody?

A

Antibodies which recognize several epitopes from unrelated antigens. (probably because the different antigens have similar structures which are recognized by a single antibody.)

44
Q

What is a domain

A

A domain is a part of a protein that is self stabilizing and which folds independently. TCR and antibodies have many domains.

45
Q

What is the structure of MHC I

A

Is largely composed of Alpha (3) domains, which anchor the receptor to the membrane and compose the peptide binding cleft. The fourth part is beta2-microglobulin

46
Q

What is MHCII

A

One half is made of beta domains with one of those being transmembrane and the other is made of beta domains one of those being transmembrane.
MHC II is larger than MHCI and has more anchor residues

47
Q

What are the components of the light chain

A

Variable, Joining, and Constant regions

48
Q

What are the components of the heavy chain?

A

Variable, diversity segment, joining region, and 3 constant regions.

49
Q

What is the difference between BCR and TCR antigen recognition?

A

BCRs bind the antigen directly and as a result recognize a.a. that are far away in the primary structure but which come together in the 3’ structure.
TCRs only have the ability to recognize 1’ continuous peptides and once more, need a MHC molecule to present the linear (unfolded) peptide chain

50
Q

What is the ligand of the T-cell receptor?

A

It is the MHC molecule and the peptide that it had bound

51
Q

Which part of MHCI is polymorphic?

A

The alpha 1 and 2 domains which form the peptide binding groove. Which makes sense this allows for wider antigen selectivity.

52
Q

What makes up the binding cleft in MHC II

A

That would be the alpha 1 and beta 1 domains. MHCII has an alpha and beta chain which are both transmembrane unlike MHC I with its non-transmembrane B2 microglobulin

53
Q

What T-cell does MHC I communicate with? What about MHCII

A

MHC I ==> CD8
-CD8 binds A1 and A3 MHC I domains
MHCII ==> CD4
-CD4 binds the B1 and B2 MHC II domains

54
Q

Where is MHC I found and what does it activate and why does this make sense?

A

MHC I are found on nearly any cell and they activate cytotoxic or cell killing T-cells. This makes sense because CD8s need to know which cells to kill and any cell has the potential to become infected.

55
Q

Where is MHC II found and what does it activate and why does this make sense?

A

MHC II activate CD4 T-helper-cells which are the activators of adaptive responses as a result MHC II is found on dendritic cells, macrophages and B cells.

56
Q

What are HV1, HV2, and HV3

A

These are hypervariable regions are the three loops which comprise the antigen binding site of antibodies

57
Q

What gene components are in a light chain? What about the heavy chain?

A

V(variable) J(Joining) and C(constant region) ==> light chain
Variable, Diversity, Joining, and Constant ==> Heavy chain

58
Q

What is an RSS and what does it look like in somatic recombination and what does it do?

A

1) Recombination signal sequence
2) It is a heptamer (7-conserved bp) separated by 12 or 23 non-conserved bp and then capped by a nonamer (9-conserved bp)
3) It makes sure that Vs don’t combo with Vs and Js don’t combine with Js ect
- 12/23 rule a 12 can only combine with a 23

59
Q

What are the VDJ recombinases and how do they work?

A

RAG-1 and RAG-2. They bring together 12/23 RSS. This forms a loop of shit which was between the two lets say V and J region which is cleaved away from the genome permanently.

60
Q

What are the broad strokes of VDJ recombination (what is the mechanism)?

A

The two segments to be joined are brought together via 12/23 rule. The bit betwixt is spliced out leaving a ds break and two hairpins. These are opened and TdT begins to add random nucleotides which are then ligated together making a impercise coding joint.

61
Q

PNP nucleotides are what

A

P ==> palindromic
-when the hairpin is cleaved this makes single strands which are palindromic.
N ==> non-template nucleotides (added by TdT)
This describes the imprecise signal joint as a result of recombination

62
Q

What genes make up the TCR

A

alpha chain: VJC

Beta chain: VJDC

63
Q

What is somatic hypermutation

A

Mutations in the antibody/antigen binding region producing clones with differences in antibody affinity. Mechanism is prefromed by activation induced cytidine deaminase (AID)

64
Q

How are MHC I molecules made and what does this one communicate with?

A

1) MHC molecules are unstable without binding their antigen.
2) MHC I is assembled in the ER. Proteins in the cytosol are cut up with the proteasome and are transported into the ER via TAP-1 and TAP-2.
3) These proteins undergo “peptide editing’ until a good fit to the MHC is found and bound and then this is transported to the PM from the ER.

MHCI communicates with CD8 in case the cell needs to be killed lest its infectious ass kill more cells.