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immunology 3 Flashcards

humoral complement microbial

1
Q

what are the two functions when an antibody has in a humoral immune response?
describe them.

A
  1. Antigen Recognition: Membrane associated antibody (IgM) is the receptor B cells use to recognize antigens. The antibodies that a B cell produces have the same specificity as the receptors on that B cell.
  2. Effector Function: Soluble antibodies are secreted by antigen-activated B cells and Plasma cells. Antibodies are the major effector molecules of humoral immunity. Different antibody types are needed for different locations and function.
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2
Q

what is an isotype?

A

It is part of an antibody.
It is the constant domain (IgG, IgM, IgE).
It determines the effector function of the Ig molecule.

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3
Q

What is an idiotype?

A

It is part of an antibody.
It is determined by the variable and hypervariable domains of the Ig molecule.
Determines the specificity of the antibody molecule.
allows it to bind to the antigen it is specific for.

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4
Q

Describe the antigen-independent phase of B cell development.

A
  1. Occurs in the bone marrow
  2. Diverse B cell receptors are made
  3. Test for a functional BCR.
  4. Select out self-reactive cells.
  5. Not dependent on specific interactions with other immune cells.
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5
Q

Describe the antigen-dependent phase of B cell development.

A
  1. Occurs in peripheral lymphoid tissue such as the spleen and lymph node.
  2. Selecting and amplifying responses.
  3. Avoid responding to peripheral self-antigen.
  4. Increase affinity to antigen.
  5. Select Ig subclass–affect effector function
  6. Generate memory cells for recall responses.
  7. Critical role of CD4 T helper cells.
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6
Q

make an overview of B cell responses in the periphery.

A

1 Microbial antigen recognition
2. Activated Th cell helps an activated B cell
3 could become a plasma cell OR undergo clonal expansion.
4. The cell can then become a memory cell or CLASS SWITCH into a plasma cell.

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7
Q

what is a subcapsular sinus?

A

in a lymph node

antigen enters the subcapsular through afferent lymphatics and gets trapped on specialized macrophages

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8
Q

what are the primary follicles?

A

It is also called a B cell zone.
B cell rich region where these cells encounter antigens.
Naive and memory B cell circulate through follicles.

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9
Q

What is the paracortex?

A

It is where the T cell are and it is where they encounter an antigen and are activated by APC–dendritic cells.

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10
Q

what are secondary follicles?

A 
It is a germinal center.
It is a consequence of the interaction between an activated B cell and an activated T helper cells.
Where class switching and affinity maturation occurs.
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11
Q

How do B cells find antigens?

A
  1. Antigen enters the nodes through the afferent lymphatics and is either trapped in the subcapsular sinus by specialized macrophages or is delivered directly to the follicles.
  2. Recirculating B cells migrate from the blood into the follicles of the lymph node.
  3. without antigen engagement, the B cell will leave the node through the efferent lymph and recirculates between and through secondary lymphoid tissues.
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12
Q

after antigen engagement what happens?

A

After antigen engagement through the B cell receptor (BCR), the B cell is activated and moves toward the paracortex.

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13
Q

what happens after b cell signaling upon antigen recognition?

A

it will stimulate different pathways which end in several different transcription factors being made to stimulate gene transcription.

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14
Q

what are features of antigens that promote B cell responses?

A
  1. Bound Complement: B Cell signaling is enhanced by complement bound to antigen–when a pathogen is coated with C3d, engagement of the CD21/CD19 complex by C3d synergizes with signaling through the B cell receptor—give stronger signaling=increase antibody response
  2. Pathogen multivalency:Many repetitive sequencing that can lead to crosslinking in receptors and a stronger response.
  3. PAMPs:Most pathogens that have PAMPs can activate PRR receptors expressed by B cells. Signaling through Toll like receptor synergizes with BCR signaling. These ligands can cause polyclonal activation of B cells.
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15
Q

what happens when a B cell binds to an antigen?

A
  1. Entry into the cell cycle
  2. low level IgM secretion (make short lived plasma cells)
  3. Express molecules that are needed in subsequent interactions with T helper cells: co-stimulatory molecules, cytokine receptors, presentation of Ag on MHC II.
  4. Migration out of follicle toward the T rich zone (increse CCR7)
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16
Q

what is the interaction between B and T cells in the lymph node?

A
  1. B cells and T cells are segregated in the lymph node.
  2. B cells encounter antigen in primary follicle. T cells encounter APC in the T-rich zone.
  3. Upon antigen recognition, both cell types modulate CCR7(molecule helps move the two together) expression and migrate towards each other.
  4. B and T cells interact at the interface of the follicle and the T-rich zone.
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17
Q

if the infected cell is infected with a viral antigen what type of B/T interaction mediated by MHC class will occur?

A

MHC I because CD8 deal with viral antigens. (endogenous)

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18
Q

if a sugar specific B cell binds to a protein will it still get T helper help?

A

Yes it will because it is still bound ad it can present with peptides to the T cell.

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19
Q

how do T cells help?

how is it maintained?

A
  1. Activation of T cells: Expression of CD40, ligand, cytokine secretion.
  2. Activation of B cell by cytokines and CD40 ligation(need CD40 ligand interaction to happen in order to get T cell help)
    A. Cognate interactions mediated by cell-cell contacts
    B. interaction occurs in a specific location at the boundary of the T-rich zone and the primary B cell follicle.
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20
Q

what are the consequences of the T and B cell interaction?

A
  1. Clonal expansion of B cells (stimulate then will divide)
  2. Establishment of germinal centers
  3. Class switching (IgM to other types)
  4. Affinity Maturation
  5. Differentiation into plasma cells.
  6. Differentiation to memory cells
    * all predicated on B cells getting help from CD4
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21
Q

how many centers do a germinal centers have? is it a part of the secondary follicle.

A

It is part of the secondary follicle.

It has a dark and light zone.

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22
Q

what is the function of a dark zone?

A

B cells undergo rapid cell division and turn on the things that leads to :

  1. Somatic hypermutation of the variable regions of the BCR
  2. Class switching
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23
Q

what is the function of the light zone?

A

Rich with follicular dendritic cells (FDCs) and CD4 follicular helper cells. B cell survival is dependent on the interaction between FDC-bound Antigen and presentation of antigen to the follicular helper t cells.

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24
Q

what is antibody affinity selection?

A

It is a process that leads to an increased affinity of antibodies for a certain antigen as a T-cell dependent humoral immune response progresses.

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25
Q

How does affinity maturation occur?

A
  1. Rapid division–After interaction with CD4, B cells will rapidly proliferate (6-12 hrs)
  2. High mutation rate–Expression of the protein AID leads to hypermutation of the V domain of the BCR
  3. Selection–B cells compete for binding of small amount of antigen displayed by (FDC). Only cells that have bound to antigen and then receive help from follicular helper t cells (binding–increased affinity over time)
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26
Q

what are the steps of an evolution in a germinal center (still associated with affinity selection)?

A
  1. Recruitment to dark zone (B cell activated)
  2. expansion
  3. Hypermutation with the help of AID, RAG1/2, CXCR5
  4. Migrate to the light zone that is aided by the expression of chemokine BLC made by FDC.
  5. Competitive selection
    a. Antigen is taken up by the FDC in the form ofimmune complexes and held in a non-degraded form for months after an infection. (FDCs+Antigen+TfH cells+ CD40L=survival signals to B cells)
    b. no binding then death
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27
Q

how do b cells undergo class switching?

A

In the germinal center
Changes a B cell production of antibody from one class (isotype) to another.
Mediated by cytokines because different helper t cells produce different cytokines and help promote switching to different isotypes.
1. cytokines make transcription from specific promoters (Il4 starts transcription from Ie)
2. Transcription starts a recombination events that result in a deletion of intervening Constant (C) genes.
3. The resulting DNA can be transcribed and translated.
4. Process makes an antibody with the same specificity but with a switched constant domain.

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28
Q

If a B cell interacts with a TH1 cells what will it interact with and what will it turn into?

A

it will interact with interferon gamma and it will cause it to switch to an IgG
(ex: IgM to IgG)

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29
Q

If a B cell interacts with a TH2 cell what will it interact with and what will it turn into?

A

It interacts with IL4, IL5, IL13 and will cause it to switch to IgE
(ex: IgM to IgE)

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30
Q

what antibodies are expressed on naive b cells?

A

IgM and IgD are both expressed as membrane receptors

*IgM is expressed as soluble antibody

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31
Q

What antibodies are expressed on activated or memory B cells?

A 
IgG, IgE, IgA are expressed on activated or memory B cells. 
All three molecules have undergone class switching and they are expressed as membrane receptors or as a soluble antibody
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32
Q

What are the effector functions of IgM?

A

Produced early upon B cell activation

Activates the classical complement pathway

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33
Q

What are the effector functions of IgG

A

The major Ig isotype in the blood
transferred across the placenta
activates the classical complement pathway
mediates neutralization and opsonization of pathogens
mediates antibody-dependent cellular cytotoxicity

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34
Q

What are the effector functions of IgA?

A

Produced in mucosal tissues and secreted into the lumen of the GI and respiratory tract
mediates pathogen neutralization
transferred to infants through breast milk

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35
Q

what are the effector functions of IgE?

A

Defense against helminths

involved in allergic responses

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36
Q

what are memory B cells?

A

they are made in germinal centers
*humoral memory to T-dependent antigens
circulate through lymphoid organs
express the affinity matured BCR on the surface
typically isotype switched (IgA or IgG)
long lived
-persistence of memory b cells after an immune response makes sure that we have an increased # of b cells needed for an antigena and ready to expand fast and turn into plasma cells and secrete antibody upon reexposure to antigen.
- provide bases for secondary Gc reactions

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37
Q

what are plasma cells?

A

they come from germinal centers in primary responses or from memory B cells in secondary responses
long lived
bone marrow, gut, lactating mammary gland
isotype switched
no receptor, no activation
make antibodies mostly

38
Q

will the secondary response of a t-dependent antigen have a faster secondary response?

A

Yes it will have a faster and better response because the T cell helped make B cells which made memory, so memory helped make it work better

39
Q

in some cases do we need t cells to develop an antibody response?

A

no. a b cell response will respond if the antigen is strong and it will respond to antigens that are repetitive better.

40
Q

what are some characteristics of t cell dependent b cell responses?

A
  1. Protein antigen
  2. slow humoral response. Activate via BCR depend on additional signals provided by T cell
  3. Will go isotype class switching
  4. will have affinity maturation
  5. will have long lived plasma cells
  6. will have memory b cells
  7. will respond to most humoral immune responses
41
Q

what are some characteristics of t cell independent b cell responses?

A
  1. multivalent antigens (bacteria with polysaccharide rich capsules
  2. fast humoral response because BCR dependent
  3. No class switching
  4. No affinity maturation
  5. Short lived plasma cells
  6. No memory cells
  7. May be needed to protect against parasites and bacteria
42
Q

will pathogens only be t-dependent or t-independent?

A

they could have both T-dependent and T-independent antigens

43
Q

will T-independent antigens have a faster second response like in T-dependent antigens?

A

no. it will have the same response because no memory

44
Q

why is the complement system called complement?

what is their function?

A

it is made up of plasma proteins called the complement proteins.
made in the liver.
act collectively to help destroy pathogens and help complement the work of antibodies?

45
Q

what are the proteins make up the classical pathway?

A 
C1
C2
C3
C4
C6
C7
C8
C9
46
Q

are the proteins active?

A

no, only active when they are cleaved. when one part broken off will it turn on.

47
Q 
how does C1 look?
how many subunits?
How many antibodies can it bind to?
which components can do enzyme activity?
if there is a lot of calcium present will C1 be there?
A

It has three components. C1q C1r and C1s.
it has 6 C1 subunits that bind to the Fc portion of an antibody when it is bound to an antigen.
Each C1q can bind to one antibody-antigen complex.
Each C1 can bind six antibodies. C1r and C1s are serine proteases and are hidden so they can’t do their enzyme activity.
C1q has no enzymatic activity.
all tied together in a calcium bow.
yes, no calcium no C1

48
Q

what happens when 2 or more C1q receptors bind to the Fc region of 2 or more antibody-antigen complexes?

A

It induces a conformational change of the C1 molecules that is now twisted and it exposes C1r and s serine protease sites.

49
Q

what happens when C1r and C1s are exposed?

A

it allows C1r to cleave C1s that activates the C1 molecule.

50
Q

what are the steps of the classical pathway?

A
  1. Activated C1 will cleave C4 into C4a and C4b. *triggered by antigen-antibody complex.
  2. C4a floats away
  3. C4b binds to the surface of the pathogen.
  4. C1 cleaves C2 into C2a and C2b.
  5. C2b floats away.
  6. C2a joins C4b on the surface of the pathogen that
    makes a complex called C4b2a–C3 convertase
  7. C3 convertase cleaves C3 into C3a and C3b.–end up
    with a lot of C3b fast.
  8. C3b is called an opsonin and helps phagocytes put a firm grip on bacteria–easier to grab a slick molecule. (opisonization=easier to coat pathogen so that macrophages can get it)
  9. Once enough C3b, some C3b bind close to C3 convertase and turn it into C4b2a3b complex–C5 convertase.
  10. C5 convertase cleaves C5 into C5a and C5b
  11. C5b binds to C6 C7 and C8 and these begin to penetrate through the pathogens cell membrane because it formed a membrane attack complex (MAC)
  12. MAC is joined by groups of C9 proteins that make a pore through the pathogens membrane.
51
Q

what are the steps of lectin binding pathway?

A
  1. triggered by mannose binding lectin protein. (mannose is found on surface of many bacterial surfaces.
  2. Mannose binding lectin protein cleaves C2 and C4.
  3. C3 convertase is made from the cleaved C4b2a
  4. C3 convertase cleaves C3 into C3a and C3b.
  5. C3b helps with opsonization.
  6. Once enough C3b, some C3b binds close to the C3 convertase and turns it into C4b2a3b complex or C5 convertase
  7. C5 convertase cleaves C5 into C5a and C5b.
  8. C5b binds to C6 C7 C8 and these penetrate the pathogens cell membrane because it formed a membrane attack complex (MAC).
  9. The MAC is formed by groups of C9 proteins that make a pore through the pathogens membrane.
52
Q

what are the steps of the alternative complement pathway?

A
  1. In the absence of C3 convertase there will be ways that C3 will be cleaved in to C3a and C3b.–always will be C3b.
  2. C3b can bind freely to whatever bacterial surfaces around.
  3. factor B will bind to C3b on the bacterial surface.
  4. factor b will be cleaved by factor d that is always active.
  5. factor b will become factor ba and factor bb.
  6. Factor ba will float off while factor bb will with C3b.
  7. The complex can now cleave as well it is now a C3 convertase and cleave C3 into C3a and C3b.–amplification step.
  8. C3b still helps with opsonization.
  9. Once enough C3b, some C3b will bind close to the C3 convertase(C3bBb) and turns it into C3bBb3b complex or C5 convertase.
  10. C5 convertase cleaves C5 into C5a and C5b.
  11. C5b binds to C6 C7 C8 and these penetrate the pathogens cell membrane because it formed a membrane attack complex (MAC).
  12. The MAC is formed by groups of C9 proteins that make a pore through the pathogens membrane.
53
Q

How is C3b regulated?

A

C1 inhibitor will dissociate Factor bb from C3b and it shuts down the alternative C3 Convertase.
Factor H will also act as a cofactor for factor 1 that can break C3b into inactive C3b (iC3b)
iC3b has no enzyme activity–can’t start alternative complement pathway.

54
Q

what type of bacteria does the MAC usually destroy?

A

gram negative bacteria

55
Q

what roles do C3a and C5a have?

A

they can act as chemotaxins that attract neutrophils, eosinophils, monocytes and macrophages.
they can also act as anaphylatoxins that help basophils and mast cells release proinflammatory molecules like histamine and heparin.

56
Q

what molecules are involved in removing antigen-antibody complexes?

A

C1, C2, C3, C4, C4

57
Q

what happens to the people who are deficient in C5 C6 C7 and C8?

A

they could have repeated neisseria infections and have a risk of gonorrhea or meningitis.

58
Q

is C9 needed to help lyse bacteria?

A

no, the MAC can do it fine on their own.

59
Q

what are the steps of a response to infection?

A
  1. Inflammatory response to infection.
  2. Detection of pathogen.
  3. Activation of immune system.
  4. APC migration to draining lymph node.
  5. APC mediated T and B cell activation (T cell differentiation, B cell Antibody class switching.)
  6. Enhance Innate immune response
  7. T and B cell effector function (humoral immunity, cell-mediated immunity)
60
Q

specifically what are the steps to an acute inflammatory response?

A
  1. tissue breach or infection
  2. complement activation and release of vasodilators, clotting factors, etc.
  3. Complement assisted phagocytosis/Mast cell activation–macrophages help.
  4. Chemotactic factors released
  5. Recruitment of innate cells because of cytokines.
  6. Containment.
  7. APC to Lymph Node
61
Q

what happens at the APC?

A

TLR will recognize DAMPs or PAMPs and it will be turned on and kinases will be turned on and numerous genes will be turned on and the include immune regulators, inflammatory cytokines, antimicrobial effector molecules, chemotactic factors, tissue repair factors.

62
Q

how can a pathogen evade the innate immune response?

A
  1. microbes with a polysaccharide-rich capsules resist phagocytosis.
  2. inhibit fusion of phagosome with lysozome (chlamydia does this)
  3. Resides in a specialized vesicle that does not undergo fusion with the lysosome (toxoplasma)
  4. Escape from the phagosome into the cytoplasm (liseteria)
  5. Outer coat resistant to digestion (TB)
  6. Inactivation of NOS (TB)
63
Q

how is the type 1 interferon and NF-kB pathway inhibited?

A

pathogens can inhibit recognition by innate immune receptors and this stops transcription of IFN genes and NF-kB genes.

64
Q

how is MHC class 1 inhibited by viral proteins?

A

The proteins can mess up the surface expression of MHC, transport of MHC to the golgi, disruption of MHC heavy chain in the ER, and transcription of MHC.

65
Q

how do extracellular bacteria evade immune mechanisms?

A

they can have: anti-phagocytic mechanisms
inactivation of complement
Genetic variation of surface antigens.

66
Q

how do intracellular bacteria evade immune mechanisms?

A

they can have:
anti-phagocytic mechanisms
inhibition of antigen presentation
antigen variation

67
Q

how do viruses evade immune mechanisms?

A 
they can:
inhibit Type 1 interferon pathway (RNA)
genetic variation of antigens (RNA)
inhibition of MHC presentation (DNA)
production of immunosomodulatory proteins (DNA)
targeting of immune cells (HIV)
68
Q

how do fungi evade immune mechanisms?

A

they can:
mask PAMPs
downregulation of complement
anti-phagocytic mechanisms

69
Q

what inhibits the classical pathways activation?

A

C1-INH

70
Q

what inhibits the classical pathways C3 convertase?

A

C4Bp and Factor I

71
Q

what inhibits the lectin pathways C3 convertase?

A

C4Bp and Factor I

72
Q

what inhibits the alternative pathways C3 convertase?

A

Factor H and Factor I

73
Q

what inhibits the formation of C5 convertase?

A

DAF,MCP,CR1, and Factor I

74
Q

what inhibits MAC?

A

S protein/Clusterin CD59

75
Q

in the alternative pathway a defect in factor D,B,P can cause what?

A

infection of pyogenic bacteria and neisseria spp. (meningitis)

76
Q

in the lectin pathway a deficiency in MBL,MASP1, MASP2, C2 and C4 could lead to?

A

Lead to increase bacterial infections–childhood

77
Q

in the classical pathway a defect in C1,2,4 can lead to what?

A

SLE and immune complex disease

78
Q

a deficiency in the C3 convertase specifically the C3b deposition can lead to what?

A

infection with pyogenic bacteria
neiserria
immune complex disease

79
Q

a deficiency in C4 convertase specifically the MAC can lead to what?

A

neiserria only

80
Q

what is paroxysmal nocturnal hemoglobinuria and how does it happen?

A

it is a disease that patients can have and it is the destruction of RBC, blood clots and messed up bone marrow function
Defect in DAF, CD59

81
Q

what happens in atypical hemolytic uremic syndrome and how does it happen?

A

it is a condition that has thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure due to glomerular thrombotic microangiopathy
Defect in MCP,Factor I or Factor H

82
Q

what is hereditary angioedema and how does it happen?

A

Episodes of edema in different body parts and it includes hands, feet, face, and airway. Swelling in the intestinal wall can lead to really bad abdominal pain, nausea, and vomiting. airway swelling=death.
Defect in C1 inhibitor (C1-INH)

83
Q

what is age-related macular degeneration?

A

it is a slow and progressive disease of the macula and it can cause irreversible vision loss.
Polymorphisms in factor H cause this to occur.

84
Q

TH1 can secrete interferon gamma and that makes the antibody switch from IgM to what?

A

IgG.

*aid gives aid to the switching

85
Q

TH2 can secrete IL4,5,13 and that makes the antibody switch from IgM to what?

A

IgE

*aid gives aid to the switching

86
Q

what is the function of IgM?

A

produced early upon B cell activation

activates the classical complement pathway.

87
Q

what is the function of IgG?

A

Transferred across the placenta
activates the classical complement pathway
mediates neutralization and opsonization of pathogens
mediates antibody-dependent cellular cytotoxicity

88
Q

what is the function of IgA?

A

produced in the mucosal tissues and secreted into the lumens of the GI and respiratory tracts
mediates pathogen neutralization
can be transferred to infants via breast milk

89
Q

what is the function of IgE?

A

defense against helminths

involved in allergic responses

90
Q

what is reperfusion injury and how does complement play a role?

A

it is cells damaged by hypoxiareoxygenation activate complement (LP)
C5a and C3a activate neutrophils to increase tissue injury
MAC damages endothelial cells

91
Q

what is an immune complex disease and how does complement play a role?

A

SLE, VASCULITIS
immune complexes deposit in vasculature and activate complement (CP)
C2a and C4a activate neutrophils and macrophages to increase inflammation

92
Q

what is a autoimmune hemolytic anemia and throbocytopenia and how does complement play a role?

A

antibody binds to erthrocytes or plates (CP)

complement activation contributes to clearance by opsonization and lysis

FMS (5 decks)

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