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DD & BL Unit 1 > Immunology > Flashcards

Immunology Flashcards

1
Q

Pattern-recognition receptor (PRR) and Toll-like Receptors (TLR)

A

PRRs are located on the surface of most body cells; they recognize various classes of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)

TLRs are a class of PRRs often found on WBCs, blood vessel endothelial cells, etc.

Especially important on DCs enabling activation of innate immune response

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2
Q

NFKB

A

The final transcription factor most commonly activated by TLR activity; mediates inflammation pathway

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3
Q

Mechanism of innate immunity

A

Dendritic Cells (DCs) located in mucous membranes recognize and ingest foreign molecules via phagocytosis; they migrate through the lymphatic system to the nearest draining node where they present the antigen via MHCII to a diverse population of lymphocytes; specifically activated lymphocytes divide and give rise to a clonal population of activated cells

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4
Q

General function of T cells

A

T cells recognize antigens that are presented by DCs; activated T cells proliferate, giving rise to a clonal population of daughter cells that travel throughout the body to places where the antigen has invaded; there, they are re-stimulated by local antigen-presenting cells to release lymphokines

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5
Q

General role of B Cells

A

B cells recognize antigens via surface receptors and become activated, with help from Tfh cells, to proliferate and produce soluble antibodies released into body fluids

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6
Q

Type I Immunopathology

A

Immediate hypersensitivity caused by overproduction of IgE in response to environmental antigen; IgE binds mast cells, triggering the release of Histamine

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7
Q

Type II Immunopathology

A

Autoimmunity

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8
Q

Type III Immunopathology

A

Occurs when an individual makes an antibody against a soluble antigen and the antigen-antibody complex, instead of being consumed by phagocytes, becomes trapped in the basement membrane of capillaries, activating the inflammatory response

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9
Q

Type IV Immunopathology

A

T-cell mediated tissue damage

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10
Q

Chronic frustrated immune response

A

Inappropriate activation of the immune response against endogenous foreign antigens, i.e. gut bacteria

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11
Q

Cytokines and chemokines

A

Small proteins released following TLR activation via NFKB pathway to produce inflammation

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12
Q

Mechanism of innate immunity

A

Dendritic Cells (DCs) located in mucous membranes recognize and ingest foreign molecules via phagocytosis; they migrate through the lymphatic system to the nearest draining node where they present the antigen via MHCII to a diverse population of lymphocytes; specifically activated lymphocytes divide and give rise to a clonal population of activated cells

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13
Q

General function of T cells

A

T cells recognize antigens that are presented by DCs; activated T cells proliferate, giving rise to a clonal population of daughter cells that travel throughout the body to places where the antigen has invaded; there, they are re-stimulated by local antigen-presenting cells to release lymphokines

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14
Q

Lymphocyte Recirculation

A

Lymphocytes circulating in the blood encounter high, cuboidal endothelial cells lining the postcapillary venules in the peripheral lymph nodes; lymphocytes pass between these endothelial cells into the body of the lymph node where they may stay or move into the lymph, which eventually drains into the venous blood

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15
Q

IgG

A

2 light chains + 2 gamma chains

Main antibody in blood; appears after IgM following immunization but concentrations go higher and last longer; activates complement; the only antibody class that can cross the placenta from mother to fetus

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16
Q

IgE

A

2 light chains + 2 epsilon chains

Mediates the immediate hypersensitivity (allergic) response; IgE Fc region binds to a receptor on mast cells triggering release of histamine

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17
Q

IgD

A

2 light chains + 2 delta chains

Receptor on B cells

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18
Q

IgA

A

2 basic units (4 light chains + 4 alpha chains) held together by a J chain and wrapped in Secretory Component

“First line of defense” - main antibody of fluid secretions; Secretory Component protects IgA from proteolysis by digestive enzymes

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19
Q

IgM

A

5 basic units (10 light chains + 10 mu chains) held together by a J chain; decavalent

The first antibody to appear in the serum after immunization; activates complement

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20
Q

Complement - Classical Pathway

A

After IgG or IgM binds antigen, a chance in Fc allows binding and activation of C1q; C1q must interact with 2 Fcs simultaneously in order to become activated, either by binding two IgGs on the same antigen or by interacting with a single IgM

C1 activates C4 and then C2, which together activate C3, which activates C5, C6, C7, C8, C9

Accumulation of C3b - C9b on the pathogen membrane forms a transmembrane pore (Membrane Attack Complex) leading to cell lysis

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21
Q

Which components of complement are lytic?

A

C3b - C9b accumulated on the pathogen membrane to form the membrane attack complex, a transmembrane pore leading to cell lysis

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22
Q

Which components of complement are chemotactic?

A

Soluble C5a is chemotactic for PMN cells

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23
Q

Which components of complement are opsonizing?

A

C3b on the pathogen surface interacts with C3b receptors on the cell surface of PMNs; C3b makes the pathogen more easily recognizable and digestible by phagocytes

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24
Q

Which components of complement are anaphylotoxic?

A

Soluble C5a can interact with receptors on the surface of mast cells, inducing them to release histamine

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25
Q

Complement - Alternative Pathway

A

Activated by IgA antigen complexes and by certain cell wall structures of microorganisms which activate complement even in the absence of an antibody response

C3 activates C5, then C6, C7, C8, C9

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26
Q

Complement - Lectin Pathway

A

The lectin pathway is mediated by mannose-binding protein (MBP) which binds carbohydrates on pathogen cell surfaces; MBP is functionally similar to C1q in the classical pathway

MBP activates C4, then C2 and C3 activates C5, which activates C6, C7, C8, and C9

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27
Q

Cross reactivity

A

The tendency of an antibody to react with more than one antigen

Ex: Streptococci bacteria cross reacts with an antigen found on heart valves; streptococci infection may activate B cells against heart valves causing complement-mediated rheumatic heart disease

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28
Q

Allotypic Exclusion

A

The process by which any individual B cell expresses only one H chain and one L chain, despite the presence of multiple copies of each; the rest of the genes are silenced (“excluded”)

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29
Q

Mechanism of V(D)J Recombination

A

First, a random D segment is brought together with a random J segment and spliced; next, a random V segment is brought together with the DJ segment and spliced; the entire region of DNA is assembled including the V(D)J unit and the constant region including the mu and delta constant region

These primary RNA transcripts are alternatively processed to make either VDJ-mu (IgM) or VDJ-delta (IgD)

When a cell wants to produce IgG, IgA, or IgE it returns to the recombined DNA constiting of the linked VDJ region and the constant region and cuts out the intervening constant sequences via splicing

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30
Q

Somatic recombination of antibodies - mechanism

A

The process by which cells increase antibody diversity through random “sloppiness” of V(D)J Recombination

Exonucleases randomly chew away a few nucleotides prior to (D)J and V segments are joined; terminal deoxynucleotidyl transferase (TdT) adds several random nucleotides to the sequence at the joining region (the N region)

2/3 times this process results in a nonsense (stop) codon and B cell destruction

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31
Q

Affinity maturation

A

Hypermutation occurs in the CDR regions of antibodies during rapid B cell division, producing both higher-affinity and lower-affinity daughter cells; over time, lower-affinity antibodies are culled and the immune response to a specific antigen improves

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32
Q

Cross reactivity

A

The tendency of an antibody to react with more than one antigen

Ex: Streptococci bacteria cross reacts with an antigen found on heart valves; streptococci infection may activate B cells against heart valves causing complement-mediated rheumatic heart disease

33
Q

Allotypic Exclusion

A

The process by which any individual B cell expresses only one H chain and one L chain, despite the presence of multiple copies of each; the rest of the genes are silenced (“excluded”)

34
Q

Mechanism of V(D)J Recombination

A

First, a random D segment is brought together with a random J segment and spliced; next, a random V segment is brought together with the DJ segment and spliced; the entire region of DNA is assembled including the V(D)J unit and the constant region including the mu and delta constant region

These primary RNA transcripts are alternatively processed to make either VDJ-mu (IgM) or VDJ-delta (IgD)

When a cell wants to produce IgG, IgA, or IgE it returns to the recombined DNA constiting of the linked VDJ region and the constant region and cuts out the intervening constant sequences via splicing

35
Q

Somatic recombination of antibodies - mechanism

A

The process by which cells increase antibody diversity through random “sloppiness” of V(D)J Recombination

Exonucleases randomly chew away a few nucleotides prior to (D)J and V segments are joined; terminal deoxynucleotidyl transferase (TdT) adds several random nucleotides to the sequence at the joining region (the N region)

2/3 times this process results in a nonsense (stop) codon and B cell destruction

36
Q

Affinity maturation

A

Hypermutation occurs in the CDR regions of antibodies during rapid B cell division, producing both higher-affinity and lower-affinity daughter cells; over time, lower-affinity antibodies are culled and the immune response to a specific antigen improves

37
Q

Allotype

A

Minor allelic differences in the sequence of immunoglobulins between individuals, determined by parental allotypes via Mendelian inheritance

38
Q

Idiotype

A

The unique combining region of an antibody, made up of the sequence of CDR amino acids of its L and H chains

39
Q

Pro B Cell

A

The earliest B-cell line differentiated cell found in the bone marrow; contains mu chains in the cytoplasm

40
Q

Pre-B cell

A

Characterized by the presence of cytoplasmic IgM but no surface expressed IgM

41
Q

Immature B cell

A

Contains both cytoplasmic and surface IgM but no IgD

If these cells become activated against antigen in the bone marrow they may undergo receptor editing and further maturation OR undergo clonal abortion

42
Q

Mature B Cell

A

Contains both surface IgM and IgD of the same specificity

43
Q

Bursa of Fabricius

A

In birds, this is the organ where B cells finish their development; it is located in the hind end of the gut

Humans have no Bursa of Fabricius; B cell differentiation takes place in the bone marrow

44
Q

IgM in fetuses & newborns

A

Fetuses make IgM in utero starting around 3 months gestation; any IgM seen in fetal circulation in utero must have been produced by the fetus because IgM cannot cross the placenta

45
Q

IgG in fetuses and newborns

A

Fetuses do not make IgG in utero and so any IgG seen in fetal circulation must have come from the mother, actively transported across the placenta; newborns start making their own IgG around ~3 months

Babies are particularly vulnerable to infection 3-6 months of age when maternal IgG has declined but their own IgG production has not ramped up yet

Premature babies born before 39 weeks gestation miss out on the sharpest spike in maternal IgG production and may be born immunocompromised

46
Q

How do Th0 cells become activated?

A

Through a “two hit” model:

  1. The Th0 cell binds the antigen-presenting dendritic cell via its TCR/CD3 complex
  2. The dendritic cell secretes IL-12, which helps to activate Th0
47
Q

Function of Th1

A

Secrete IFN-y, which activates M1 macrophages through the classical pathway; M1 macrophages phagocytose foreign material

Secretes IL-2, which activates CTLs

48
Q

Function of Th17

A

Activates M1 macrophages through the classical pathway

49
Q

Function of Th2

A

Releases IL-4, which activates M2 macrophages through the alternate pathway; M2 macrophages participate in tissue healing and walling off of pathogens

IL-4 is also chemotaxic for eosinophils

50
Q

Function of Tfh

A

Activated Tfh migrate to the lymph node follicle where they stimulate B cells to secrete antigen and facilitate antibody class switching from IgM / IgD to IgG, IgA, and IgE

51
Q

Function of Treg

A

Releases TGF-B and IL-10, which function to negatively regulate the immune response by inhibiting Th0

52
Q

Activation of CTLs

A

CTLs are activated by antigen-presenting dendritic cells and also by IL-2 secreted by Th1

53
Q

Functions of CTLs

A

CTLs induce apoptosis by 2 mechanisms:

  1. CTLs express CD95L, which interacts with CD95 on the surface of target cells to induce apoptosis
  2. CTLs secrete proteases called granzymes and perforins, which allow penetration of granzymes into the cell, causing apoptosis
54
Q

Structure of TCRs

A

TCRs are comprised of two transmembrane domains, alpha and beta; each chain has 3 CDRs

TCRs associate closely with CD3 on the surface of all T cells, which facilitates its binding interactions with antigens

55
Q

Cross-presentation

A

Dendritic Cells can present antigen on either MHC-I or MHC-II, allowing DCs to activate both CTLs and Th cells simultaneously

56
Q

How do Thf cells activate B cells?

A

B cells take up, digest, and present a piece of their specific antigen on MHC-II, which is recognized by Tfh cells; Tfh then directs specific activating signals toward the B cell, inciting it to release antibody or undergo class switching

57
Q

T cell independent antibody response

A

Some antigens do not require T cell help to produce an immune response; these are mostly carbohydrates with the same epitope repeated over and over, which can bind multiple sites on IgM

Since no T cells are involved class switching cannot occur and the immune response is mediated entirely by IgM

Even individuals who are extremely T cell deficient can make some immune response to carbohydrates

58
Q

Mitogen

A

A molecule that stimulates T cell division

ex: Phytohemagluttinin (PHA), Pokeweed mitogen

59
Q

AIRE

A

Autoimmune regulatory element; responsible for the presence of otherwise out-of-place peptides in the thymus which help facilitate negative selection of developing T cells that are auto-reactive against a wide variety of self peptides

60
Q

Positive Selection of T Cells

A

Occurs via interactions between alpha and beta CDRs 1 and 2 with MHC-I (for CTLs) or MHC-II (for Th cells)

61
Q

HLA Alleles by Class

A

Class I: B / C/ A

Class II: DP / DQ / DR

62
Q

One way MLR

A

Donor leukocytes are treated with radiation to kill dividing T cells, while leaving donor macrophages with MHC-II intact; donor leukocytes are mixed with recipient leukocytes; any growth in T cell division is the result of recipient T cells activating against donor MHC-II

63
Q

H-Y

A

H-Y is an internal protein coded for on the Y chromosome whose peptides are displayed on MHC-I of all male cells; because of H-Y, male skin gracts will be slowly rejected by females, while males can accept female skin grafts

64
Q

Hyperacute graft rejection

A

Occurs if a graft is given to a patient who has a preexisting antibody, IgG or IgM, to it (either to its HLA because of prior graft or, in a mismatch, to ABO blood group antigens)

65
Q

Mechanism of graft rejection

A

Th1 cells recognize foreign HLA-DR on graft cell macrophages causing them to proliferate and secrete IFN-y, which activates M1 macrophages;

Meanwhile, CTLs recognize HLA-A and HLA-B (Class I) on all graft cells; however, this recognition is usually insufficient to activate CTLs without the help of Th1-derived IL-2 as a second signal. Once activated, CTLs start directly killing graft cells.

66
Q

Why is DR the most important histocompatibility locus?

A

If DR is identical between donor and recipient then Th1 cells will not be activated; as a consequence, few M1 macrophages will be activated, no IL-2 will be generated, and few CTLs will be activated

67
Q

Ankylosing Spondylitis

A

An arthritic condition involving inflammation of the tendons and fibrous joints, leading to calcification and inflexibility of the joints

92% of people with AS are HLA-B27; the current model suggests that rare self-modification of proteins may create novel epitopes that associate strongly with certain MHC alleles; the T Cells that respond to these “neo-antigens” cross-react with the normal protein

68
Q

Types of Immunity

A

Natural / Active - immunity resulting from exposure to disease

Natural / Passive - immunity transferred from mother to fetus (IgG across placenta, IgA in breastmilk)

Artificial / Passive - anti-serum (serum containing purified antibodies, already produced)

Artificial / Active - vaccination (synthesized antigen presentation), allows body to produce antibody

69
Q

Tetanus Immunization

A

Tetanus toxin is so toxic that it cannot be safely administered; tetanus toxoid (inactivated toxin) resembles the toxin enough to produce immunogenic response

Antibiotics are only partially effective against tetanus because its the release of toxin, not the growth of bacteria, that is responsible for pathology

Antitoxin (human tetanus immune globulin) can be used but is not widely available

70
Q

Conjugate vaccines

A

Created by covalent linkage of a poor antigen (usually polysaccharide organisms that activate T-cell independent immune response) with a carrier protein from the same micro-organism to which Tfh cells can respond and help focus the B-cell response

71
Q

Adjuvant

A

Substances added to vaccines to make them more immunogenic

Mechanism: Adjuvants mimic PAMPs and thereby help cause an innate immune response through activation of DCs and subsequent Tfh proliferation

Ex: Alum

72
Q

People deficient in complement are susceptible to infection by what organism?

A

Neisseria Gonorrhoeae

73
Q

Left Shift

A

Leukocytosis with an increase in the number of immature leukocytes in the blood, particularly bands (neutrophils)

74
Q

Schilling Test

A

Tests for pernicious anemia due to B12 malabsorption;

Radiolabeled B12 is given orally and is followed by IM injection of B12 to saturate B12 receptors in the tissue so that any radiolabeled B12 that is absorbed from the gut is excreted into the urine.

A normal result shows at least 10% of the radiolabeled vitamin B12 in the urine over the first 24 hours.

75
Q

Which part of the membrane attack complex polymerizes to form a transmembrane channel?

A

C9

76
Q

What is the half life of maternal IgG?

A

3 weeks

77
Q

Live attenuated vaccines

A

MMR
Flu nasal spray
Chicken Pox
Rotavirus

Only to be given after 1 year age

78
Q

What is an average value for cellularity?

A

100 - age (%)

DD & BL Unit 1 (6 decks)

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