Exam 3: Humoral Immune II Flashcards

1
Q

what do naïve B cells express that function as antigen receptors

A

IgM

IgG

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2
Q

what happens every time there is an immune response from the same antigen

A

antibodies have a higher affinity for the antigen

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3
Q

Do secreted antibodies have the same specificity as that of the naïve B cell membrane receptors that recognize antigens?

A

Yes

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4
Q

how many plasma cells to B cells generate once activated?

how many antibodies can they produce a day?

A

Once activated B cells can generate up to 4000 plasma cells

Can produce up to 10^12 antibody molecules per day

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5
Q

what is heavy chain isotype (class) switching

A

Some B cells may begin to produce antibodies with different heavy chain isotypes (classes), which mediate different effector functions and are specialized to combat different types of microbes

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6
Q

What is affinity maturation

A

repeated exposure to an antigen results in the production of antibodies with increased affinity

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7
Q

High affinity antignes

A

fit properly with antigen-binding site

maximum number of interactions occur

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8
Q

B cell co-receptors

A

bind to fragments of complement proteins and deliver an additional signal to the B cell nucleus

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9
Q

CD19 and CD21 interaction

A

when CD21 binds to CD19 –> increased activation of CD19

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10
Q

B cell travel through lymph nodes

A

Naive B cells leave bone marrow via blood

May encounter antigens in blood, lymph, or lymph nodes

If they don’t bind to an antigen or fail to find the correct Th cell they leave via efferent lymphatic vessels and move on to next lymph node

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11
Q

What are HEVs

A

specialized venules inside lymph nodes and peyer’s patches that have receptors for cell-surface proteins on T and B cells

This interaction allows T and B cells to exit the blood and enter lymph nodes

Inside Th cells encounter antigen presenting dendritic cells

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12
Q

Antigen processing and presentation by B cells inside Lymph Node

A

Mammalian B cell BCRs bind to antigen. Then via receptor mediated endocytosis, internalize the antigen-antibody complex.

The newly formed endosomes fuse with the lysosomes that contain both proteolytic enzymes and MHC II molecules.

The antigenic peptides bind to the MHC molecules and the MHC-antigen complexes return to the surface for presentation to Th cells.

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13
Q

B cells proliferate in lymph nodes germinal centers

A

After activation in the medulla, a large population of B cells moves to lymphoid follicles, proliferate, and form germinal centers

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14
Q

what are dividing B cells called

what are resting B cells called

A

dividing B cells - centroblast

Resting B cells - centrocytes

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15
Q

what types of cells do germinal centers contain

A

Centroblasts

Centrocytes

Th cells

Follicular dendritic cells

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16
Q

what happens to B cells in germinal centers

A

B cells undergo isotype switching and somatic hypermutation

Then emigrate the lymph node and differentiate into plasma cells that migrate to bone marrow

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17
Q

how to plasma cells leave the lymph node

A

efferent lymphatic vessels

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18
Q

what do plasma cells do

what do memory cells do

A

Plasma cells - produce antibodies

Memory cells - APC in secondary immune response

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19
Q

Primary immune response

A
  1. First injection
  2. Naive B cell
  3. Activated B cells
  4. Antibody secreting cells in peripheral lymphoid tissues - plasma cells
  5. IgM production
  6. Long lived plasma cells in bone marrow
  7. Memory B cell
20
Q

Secondary immune response

A
  1. Second injection
  2. Memory B cells
  3. Antibody secreting cells –> plasma cells
  4. IgG production
  5. Long lived plasma cells in bone marrow
  6. Memory B cell
21
Q

differences between primary and secondary immune response

A

Primary - IgM, lower antibody production, slower antibody production

Secondary - memory B cells, IgG, higher antibody production, faster antibody production

22
Q

Effector mechanisms of antibodies - bacterial toxins

A
  1. Specific antibody
  2. Bacterial toxins
  3. Cells with receptor for toxins
  4. Neutralization
  5. Ingestion by macrophage
23
Q

Effector mechanisms of antibodies - bacterial in extracellular space

A
  1. Specific antibody
  2. Bacteria in extracellular space
  3. Macrophage
  4. Opsonization
  5. Macrophage with Fc receptor
  6. Ingestion and lysis by macrophage
24
Q

Effector mechanisms of antibodies - Bacteria in plasma

A
  1. Specific antibody (IgM or IgG)
  2. Bacteria in plasma
  3. Complement activation - classical pathway
  4. Complement fragmentation
  5. Ingestion and lysis
25
Q

how is the ability of a receptor to bind to an antigen determined

A

the shape of its binding site

Shape –> folding of peptide chain –> amino acid sequences

26
Q

where is the information needed to make proteins, including antigen receptors, located

A

the gneome

27
Q

how many antigen binding receptors on B and T cells can mammals express (produce)

A

up to 10^15 different antigen binding receptors on B and T cells

28
Q

How many genes to antigen binding receptors use

A

fewer than 500 genes

29
Q

How many genes code for the variable region

How many genes code for the constant region

A

Several genes code for variable region

One gene codes for constant region

30
Q

what contributes to gene diversity

A

Gene recombination

Somatic mutation

Gene conversion

31
Q

Number of constant genes in B cell receptors

A

5

1 gene codes for IgM
1 gene codes for IgG
1 gene codes for IgE
1 gene codes for IgA
1 gene codes for IgD
32
Q

how are antigen receptor genes coded

A

Antigen receptor genes are coded for by 3 genes originating in 3 widely separated groups.

The genes for a complete receptor chain are assembled by joining one gene selected from each group.

Variable genes - hundreds
Joining genes - tens
Constant gene - one

33
Q

How many distinct light chain loci

A

2

1 coding for kappa chains
1 coding for lambda chains

these are located on different chromosomes

34
Q

which antibody is produced first

A

IgM (mu gene)

35
Q

which antibodies do all B cells have

A

IgM (mu gene)

IgD (delta gene)

36
Q

Which antibody is mainly produced in secondary immune response

A

IgG (gamma gene)

37
Q

gene recombination

A

deleting unwanted genes by looping out

unwanted genes form a loop that is then cut off by a recombinase enzyme and the cut ends are joined together

38
Q

gene recombination - construction of an immunoglobulin light chain

A

selected V and J genes are joined as intervening genes deleted

VJ and C genes remain separated until RNA splicing occurs

intervening RNA segments are deleted leaving V, J, and C genes together in the mRNA

DNA rearrangement occurs during early B cell development so each individual B cell is committed to making a single form of light chain for its antigen receptor

39
Q

gene recombination - heavy chain construction

A

2 DNA rearrangement events are required to link V, D, and J genes together

first rearrangement event joins selected D and J genes

second rearrangement event adds selected V gene

finally unwanted J genes are excised and VDJ joined to C in the mRNA

40
Q

Gene recombination - B cell development

A

during development, each B cell has 4 attempts to make a productive gene rearrangement coding for a functional immunoglobulin

if it fails all 4 attempts - apoptosis

1st attempt - first IGK gene rearrangement
2nd attempt - second IGK gene rearrangement
3rd attempt - first IGL gene rearrangement
4th attempt - second IGL gene rearrangement

41
Q

How are CDR1, CDR2, and CDR3 formed on immunoglobulin light chain

A

CDR1 and CDR 2 - formed by somatic mutation or gene conversion

CDR3 - formed by recombination of V and J gene segments

42
Q

how are CDR formed on TCR

A

CDR - formed by recombination of V, (D), and J gene segments

no somatic mutation

43
Q

what is the major difference between the variable regions of the TCR and immunoglobulins

A

formation of CDRs

immunoglobulins have 3 CDRs
CDR1 and CDR2 - somatic mutation
CDR3 - gene conversion

TCR - somatic mutation is stringently avoided to prevent self reactivity

44
Q

why is somatic mutation avoided in variable region of TCR

A

to prevent self reactivity

45
Q

selection of somatic mutants

A

spontaneous mutation during expression of a B cell clone results in development of cells with antigen receptors that differ in affinity for antigen

cells that bind antigen strongly will be more intensely stimulated than cells that bind it weakly

as a result of this selection pressure, the B cell population gradually increases its binding affinity during the course of an antibody response

if a mutation creates a B cell with reduced antigen binding - apoptosis

46
Q

gene conversion

A

in this process segments of upstream genes or pseudogenes are inserted into a single V region to generate sequence diversity

47
Q

where does gene recombination happen in T cell receptor

A

gene recombination only in variable region