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immunology lecture 22 key points

front 1

what is a variant?

back 1

a virus whose genome sequence differs (varies from a reference virus

front 2

what is a strain/serotype?

back 2

a variant that possess unique and stable phenotypic characteristics; also referred to as a serotype

front 3

what is antigenic drift?

back 3

selection favors those strains that don't illicit a strong immune response

coupled with antigenic original sin, it means that response can be very different

the accumulation of minor genetic changes

front 4

what is antigenic shift?

back 4

simultaneous infection of pigs with both human and avian influenza strains leads to a unique new strain of virus

the human population is entirely unprepared

front 5

what is gene conversion?

back 5

when a trypanosome infects a human, it will replicate before adaptive immunity can fight it. most of the resulting trypanosomes will express the same dominant VSG

chronic cycle of antibody production and antigen clearance leads to immune complex deposition and heavy inflammation

eventually neurological damage results and the individual falls into a coma

malaria uses a similar evasion strategy

front 6

what is VSG?

back 6

variable surface genome, only one of those variants can be expressed at a time

front 7

what is superantigen?

back 7

a molecule that, by binding nonspecifically to MHC class II molecules and T cell receptors, stimulates the polyclonal activation of T cells

front 8

how does a superantigen work?

back 8

usually, they contain binding sites that allow them to cross-link MHC class II (on the APC) as well as the antigen receptor and CD28 (on the CD4+ T cell)

results in non-specific activation of CD4+ T cells and excessive amounts of IL-2, IFNy, and TNFa

front 9

primary immunodeficieny

back 9

an immunodeficiency resulting from an inherited defect in immune development or function

loosely categorized by effects innate or adaptive responses; grouped by the specific components they affect

all immune components (innate or adaptive, humoral or cell-mediated) can be affected

nature of innate immune defect will determine which pathogens are most problematic

front 10

what are the warning signs of primary immunodeficiency?

back 10

early detection is key for primary immunodeficiency

recurrent infections are often an indication

can be difficult to detect based on the presence of maternal antibodies

if there is cause for concern the response to vaccines can be monitored

newborn blood samples are screened for TCR excision circles

front 11

secondary immunodeficiency

back 11

a condition where the immune system becomes compromised due to external factors, such as infections like HIV/AIDS, malnutrition, certain medications like chemotherapy, or chronic illness

front 12

what is an opportunistic infection?

back 12

an infection that takes place when a pathogen only cause serious illness in individuals with a weakened immune system

front 13

what is SCID?

back 13

severe combined immunodeficiency

stems from genetic defects leading to a lack of T cells in the periphery

defective differentiation of myeloid and lymphoid lineages from HSCs

defective cytokine signaling in T-cell progenitors

defects in purine metabolism

rearrangement defects caused by RAG1, RAG2, or other proteins involved in gene rearrangement

signaling defects of pre-TCR or TCR

front 14

what causes SCID?

back 14

reticular dysgenesis

ADA deficiency

impaired RAG1/2

disruption of genes for cytokine signaling

disruption of the genes involved in pre-TCR and pre-TCR signaling

front 15

bare-lymphocyte syndrome

back 15

no MHC class II molecules

lack of positive T cell selection events

impaired peripheral helper T cell responses

front 16

defective MHC class I expression

back 16

mutated TAP genes

impaired positive selection of CD8+ T cells

heightened susceptibility to viral infections

front 17

hyper IgM syndrome

back 17

deficiency in CD40L impairing communications between helper T cells and APCs

impairs interactions between B cells and helper T cells leading to limited production of antibodies to T-dependent Ag

production of Ab to T-independent Ag not affected, leading to high levels of IgM

front 18

hyper IgE syndrome

back 18

characterized by skin abscesses, recurrent pneumonia, eczema, and high levels of IgE

may be accompanied by facial abnormalities and bone fragility

induced by STAT3 gene mutation

causes dysregulation of TH pathways, particularly TH17

front 19

CVID

back 19

common variable immunodeficiency disorders

several defects induce this problem

allows recurrent infections due to immunodeficiency

one or more antibody levels are seriously reduced, though B cell numbers are usually normal

front 20

X-linked agammaglobulinemia

back 20

extremely low levels of IgG, absence of other isotypes, causes recurrent bacterial infections

caused by a defect in Bruton's tyrosine kinase required for BCR signal transduction

B cells are locked in the pro- to pre-B cell stage in the bone marrow

disease managed by antibiotics and passive antibodies

front 21

leukocyte adhesion deficiency

back 21

caused by an abnormality in the gene for the common B chain of inegrin adhesion molecules

limits leukocyte recruitment to inflamed areas

higher susceptibility to bacterial and fungal infections

severity of defect varies for unknown reasons

front 22

chronic granulomatous disease

back 22

defect in NADPH oxidative pathway used by phagocytes to generate ROS

results in more bacterial/fungal infections and higher degrees of inflammation responses that produce granulomas

treatment relies on anti-fungal/antibacterial drugs

front 23

general complement deficiency

back 23

C4 defects: generalized failure to activate complement

alternative pathway failure: failure of entire pathway

often results in greater likelihood of bacterial/fungal infections

front 24

IPEX

back 24

mutated and inactive FoxP3 gene preventing development and function of T(REG) cells

allows autoreactive T cells that escape the thymus to go unchecked

immune destruction of bowel, pancreas, thyroid, skin can result in death before 2 years of age

front 25

APECED

back 25

caused by a mutation in the AIRE gene for autoimmmune regulatory activities

allows escape of autoreactive T cells from the thymus, causing organ-specific autoimmunity

front 26

replacement therapy

back 26

passive Ig injection

production and injection of recombinant protein

front 27

gene therapy

back 27

replacement of missing or defective gene

front 28

bone marrow transplantation

back 28

replacement of missing cell type or lineage

front 29

what are the causes of secondary immunodeficiency?

back 29

acquired hypogammaglobulinemia

agent-induced immunodeficiency

infectious disease

front 30

how is HIV spread?

back 30

intimate contact with infected body fluids

vaginal/anal intercourse

receipt of infected blood/blood products

passage of HIV from mother to infant

front 31

what are the important structural components of HIV?

back 31

RNA retro-virus

expresses gp120 and gp41 glycoproteins

preferentially infects CD4+ T cells

binds CD4 and then CXCR4 and/or CCR5

front 32

what are the three structural genes of HIV?

back 32

gag

pol

env

front 33

what are the three phases of HIV infection?

back 33

acute phase

asymptomatic phase

AIDS

front 34

what are the targets of HAART?

back 34

chemokine receptor antagonists

fusion inhibition

RT inhibition

integrase inhibition

protease inhibition

front 35

what are some of the challenges to finding an HIV vaccine?

back 35

a vaccine is hard to produce

virus mutates rapidly

trials have been ineffective

dangers of testing attenuated vaccines