Genetics Week 8

Front 1

Innate system, 3 major components.

Back 1

• Innate immune system includes the elements of the early phase of the immune response
– phagocytes (a cell that engulfs and destroys the microorganism)
– complement system (which destroys microbes by perforating their cell membranes)
– Natural killer cells (special lymphocytes; NK cells) respond to viruses and some tumor cells.

Front 2

Adaptive immune system, major componenets

Back 2

B lymphocytes (B cells)

T lymphocytes (T cells)

Humoral immune system

Front 3

How many antibodies is each plasma cell capable of secreting?

Back 3

Each plasma cell is capable of secreting 10 million antibodies per hour.

Front 4

What is an antigen?

Back 4

On the surface of a pathogen. Antibodies attach to antigens.

Front 5

The maturation of B cells into antigen producing plasma cells takes how long?

Back 5

5 to 7 days

Front 6

B lymphocytes (B cells), function?

Back 6

B lymphocytes (B cells) secrete circulating antibodies (immunoglobulins) that fight infection (also called the “humoral immune system”); mammals, immature B cells are formed in the bone marrow; when mature, the B cell becomes an antibody-secreting plasma cell.

Front 7

T lymphocytes (T cells) , function

Back 7

T lymphocytes (T cells) assist B cells and can directly kill infected cells (also called the “cellular immune system”) develop from the Thymus

Front 8

The B Cell Response:

Back 8

Humoral immune system: foreign particles are displayed via class II MHC molecules on antigen presenting cells (phagocytes and B-lymphs; macrophages and dendritic cells) these are recognized by helper T cells which stimulate proliferation of B cells whose immunoglobulins can bind to the foreign pathogen.

Front 9

What are memory B cells?

Back 9

A subset of high-affinity binding B cells, persist in the body after infection has ended. These cells, provide a more rapid response if the pathogen is encountered again.

Front 10

___________ is capable of destroying the body’s cells once they are infected; peptides from the pathogen are displayed on cell surfaces by _____________; these are recognized by _____________ which destroy the infected cell.

Back 10

Cellular immune system

class I MHC molecules

cytotoxic (killer) T cells

Front 11

What are TH1 cells?

Back 11

Secrete cytokines, which stimulate cytotoxic T lymphocytes. These cytotixic T lymphocytes bind to the foreign peptides on the surfaces of the infected cells.

Front 12

What are TH2 cells?

Back 12

Secrete interleukins 4 and 5, which stimulate B cells whose receptors can bind to the foreign peptide.

Front 13

What are regulatory T cells?

Back 13

Helps to regulate the immune system so that self peptides are not attacked.

Front 14

Immunoglobulin molecular structure, describe structure.

Back 14

Immunoglobulin molecular structure consists of four chains: an identical pair of longer heavy chains and an identical pair of shorter light chains; all are linked by disulfide bonds

Each heavy and light chain contain a constant and a variable region

Front 15

What determines which class an Ig belongs to?

Back 15

The 5 types of heavy chains (of a immunogobulin) (G, A, M, D, E).

Front 16

heavy and light chains contain what two regions?

Back 16

Each heavy and light chain contain a constant and a variable region

Front 17

Function of variable region?

Back 17

Variable region varies within Ig classes and is responsible for antigen recognition and binding

Front 18

Function of constant region?

Back 18

constant region activates complement and phagocytes

Front 19

What are the two types of light chains?

Back 19

Kappa and lambda

Front 20

How do you get multiple germline immunoglobulin genes?

Back 20

during meiotic recombination, immunoglobulin genes are recombined to give certain amount of diversity

Front 21

VDJ rearrangement, define

Back 21

V(D)J recombination nearly randomly combines Variable, Diverse, and Joining gene segments in vertebrate lymphocytes,

mechanism of genetic recombination in the early stages of immunoglobulin (Ig) and T cell receptors (TCR) production of the immune system.

Front 22

Somatic hypermutation

Back 22

SHM diversifies B cell receptors used to recognize foreign elements (antigens) and allows the immune system to adapt its response to new threats during the lifetime of an organism.

a change in mutation rate of heavy chain genes in maturing B-cells

Front 23

What is affinity maturation?

Back 23

Only a small subset of B cells have cell-surface receptors (immunoglobulins) that can bind to a specific foreign antigen.



Once these B cells are stimulated by foreign antigen, they undergo affinity maturation—somatic hypermutation of the V segments of immunoglobulin genes.

Enzyme: activation-induced deaminase, causes cytosine based to be replaced by uracil.

affinity maturation is the process by which B cells produce antibodies with increased affinity for antigen during the course of an immune response

Front 24

What enzyme is involved in somatic hypermutation?

Back 24

Enzyme: activation-induced deaminase, causes cytosine based to be replaced by uracil

Front 25

What is the mutation rate of somatic hypermutation?

Back 25

about 10^-3 per base pair per generation

Front 26

What is the result of somatic hypermutation?

Back 26

Causes a lot of variation in DNA that codes for immunoglobulin. SHM diversifies B cell receptors used to recognize foreign elements (antigens) and allows the immune system to adapt its response to new threats during the lifetime of an organism

Front 27

Major histocompatibilty complex, describe genetics?

Back 27

encoded for by 100 expressed genes on chromosome 6p

Front 28

Class I MHC, describe.

Back 28

heavy glycoprotein chain
and a light chain called beta-2 microglobulin
contains the highly polymorphic HLA A, B,and C loci on Chromosome 6 (important in cell recognition and transplantation)

these stimulate killer T-cells

Front 29

Class II MHC, describe.

Back 29

heterodimers that are on the surfaces of antigen-presenting cells;

located on Antigen presenting cells; stimulate T helper cells.

genes contain the HLA DP, DR, and DQ complexes that transport proteins to the ER and are highly polymorphic (most polymorphic loci known in humans)

Front 30

Class III MHC

Back 30

complement proteins

Front 31

MHC restriction

Back 31

MHC restriction: T cells only recognize peptides that are on MHC molecules.

Front 32

Killer cell immunoglobulin-like receptors (KIR)

Back 32

Some viruses and tumors suppress MHC, so that they cannot be detected by T cells. But in absence of MHC, Natural Killer cells are activated. NK activation is controlled by KIR. KIR inhibits NK cells when NK cells bind to MHC class I on normal cells. And KIR activates NK cells when MHC class I are absent.

Front 33

Antibodies for: A, AB, B, O

Back 33

A antigen- have anti-B antibodies
B antigen- have anti-A antibodies
AB antigen--no A or B antibodies
O --no antigen-- have anti A and anti B antibodies.

Front 34

For Rh, DD, Dd, and dd has what antigens?

Back 34

DD and Dd--has Rh antigen, is Rh +

dd -- Rh negative and do not have Rh antigen.

Front 35

What percentage of North Americans are Rh positive? And Rh negative?

Back 35

85% are Rh positive
15% are Rh negative.

Front 36

erythoblastosis fetalis, describe.

Back 36

Anti-Rh antibody production requires stimulus by the human Rh antigen itself. An Rh-negative person does not produce anti-Rh antibody unless he is exposed to Rh antigen.

Problems when child is Rh+ fetal blood enters Rh- mother blood, and mother produce anti-Rh antibodies. If mother has second child, her Rh antibodies attack fetal blood.

Fetus becomes anemic and releases erythroblases into blood stream. – erythoblastosis fetalis.

Front 37

What percentage of North Americans of European descent matings are Rh incompatible?

Back 37

13%

Front 38

Primary vs secondary immunodeficiency diseases

Back 38

Primary immunodeficiency diseases: are caused by abnormalities in cells of the immune system and are usually produced by genetic alterations. More than 100 different primary immunodeficiency syndromes have been described.

Secondary Immunodeficiency: occurs when components of the immune system are altered or destroyed by other factors, such as radiation, infection, or drugs. ex: AIDS.

Front 39

B-Cell immuniodeficiency diseases, makes patients susceptible to what?

Back 39

Render the patient especially susceptible to recurrent bacterial infections such as Streptococcus pneumonia.

Front 40

agammaglobulinemia (XLA)?

Describe this disorder, whom does it usually affect, what causes it, what is it categorized as?

Back 40

Patients with XLA lack B cells and have no IgA, IgE, IgM, IgD in their serum. Caused by mutations in the gene (BTK) that encodes a B cell thyrosine kinase necessary for normal B cell maturation. majority males.

B-Cell immuniodeficiency diseases

Front 41

T-Cell immunodeficiency diseases, affect what?

Back 41

directly affect T cells, but they also affect the humoral immune response, because B cell proliferation largely depends on helper T cells. Thus patients develop severe combined immune deficiency (SCID) and are susceptible to many opportunistic infections such as Phenumocystis jirovec

Front 42

What are the causes of SCID, what genes is affected, how do they interact with T cells, what is the treatment?

Back 42

1/2 caused X linked recessive mutations in a gene encoding the y chain that is found in some cytokine receptors. Without these receptors, T and NK cells do not get signal. These receptors rely on Jak3. Without Jak3, person gets SCID

About 15% of SCID caused by adenosine deaminase (ADA) deficiency. ADA is an aitosomal recessive metabolic disorder, results in a buildup of metabilites that are toxic to B and T.

SCID can also result from mutations in RAG1 and 2, two genes involved in VDJ recombination and formation of T and B cell receptors.

Front 43

What is Bare Lymphocyte syndrome? The gene, the how does it affect class I MHC molecules and class II?

Back 43

Immune defect, result in lymphocytes that lack MHC molecules on surface. Mutation in TAP2 gene.

Front 44

What is chronic granulomatous disease (CGD)? What is the cause, the gene, affects.

Back 44

Primary immunediffency disorder, in which phagocytes can ingest bacteria and fungi but cannot kill them. Leads to a constant cellular immune response, leading to formation of granulomas. Most common cause is X linked mutation.

Front 45

A number of syndromes include immunodeficiency as one of their features, list 3 and describe how the immune system is affected

Back 45

DiGeroge, T cell deficenty
Wiskott-Aldrich, deficency in platlets and B and T cells. Mutation in WAS gene.
Bloom syndrome