Loading presentation...

Present Remotely

Send the link below via email or IM

Copy

Present to your audience

Start remote presentation

  • Invited audience members will follow you as you navigate and present
  • People invited to a presentation do not need a Prezi account
  • This link expires 10 minutes after you close the presentation
  • A maximum of 30 users can follow your presentation
  • Learn more about this feature in our knowledge base article

Do you really want to delete this prezi?

Neither you, nor the coeditors you shared it with will be able to recover it again.

DeleteCancel

The Genetics of Immunity

No description
by

Ryan Bronson

on 7 April 2015

Comments (0)

Please log in to add your comment.

Report abuse

Transcript of The Genetics of Immunity

Abnormal Immunity
Altering Immunity
The Human Immune System
a network of vessels called lymphatics
B cells and T cells are two major types of lymphocytes
genetic connection is the proteins required to carry out an immune response

Crowd Diseases
epidemics start with a pathogen entering a population that hasn’t encountered it before
crowd diseases used to travel with people, as populations expanded to the new world and traveled along trade routes
now spread through air travel
usually vanish quickly
due to: vaccines, treatments, altered behavior, eliminated population

Bioweapons
inhalation anthrax
genome encodes three proteins
one binds to macrophages and admits other proteins
one overloads signal transduction and impairs the cell’s ability to engulf pathogens
one breaks open macrophages, which release tumor necrosis factor and interleukins

The Genetics of Immunity
Acquired Immune Deficiency Syndrome (AIDS)
acquired by infection with HIV
HIV genome
the virus enters macrophages
facilitates viral infection
reverse transcriptase reverts RNA into DNA
viral DNA is transcribed and translated
T cells begin dying at a rapid rate, the body is susceptible to bacterial infection
cytotoxic T cells are also killed
HIV replicates quickly, changes quickly, and can hide
mutates easily
errors occur every 1 in 5,000 bases
antibodies can’t keep up with mutations
variants resistant to AIDS drugs, leading to a “cocktail”

Autoimmunity
The Importance of Cell Surfaces
Overview
Adaptive Immunity
“self” or “nonself”
mutations can impair immune function
genes confer susceptibilities and resistances to different infectious diseases
antibodies and cytokines
antigens
genes specify the cell surface antigens
Blood Groups
29 major blood types
blood transfusions are matched based on antigens

Major Histocompatibility Complex
located on chromosome 6
70 genes, 50% of genetic influence on immunity comes from MHC
three classes
class I and II encode the human leukocyte antigens (HLAs)
class I includes three genes that vary greatly and are found on all cell types and three genes are are more restricted in their distribution
class II includes three major genes whose encoded proteins are found mostly on antigen-presenting cells
MHC class III genes encode proteins that are in blood plasma and that provide nonspecific immune functions

Human Leukocyte Antigens (HLAs)
2 in 20000 unrelated people match for the six major HLA genes
organ/blood/tissue donors
now very complex
certain disorders associated with inheriting particular HLA types
ankylosing spondylitis inflames and deforms vertebrae

Innate Immunity and Physical Barriers
Physical Barriers and Inflammation
unbroken skin, mucous membranes, stomach acid
broad, rapid response
inflammation at an injury site
sends cells
plasma accumulates
increased blood flow

Important Proteins
the complement system: plasma proteins that assist other defenses

collectins: broadly protect against bacteria, yeast, and some viruses

cytokines:
interferons
interleukins
tumor necrosis factor
colony-stimulating factor

Overview
must be stimulated into action
B cells and T cells differentiate
humoral immune response
cellular immune response
adaptive immunity is diverse
specific responses for different pathogens
remembers pathogens previously encountered by the immune system
first contact: primary immune response
next contacts: secondary immune response, memory-based
mutated pathogens (cold and flu)

The Humoral Response: B Cells and Antibodies
an antigen-presenting macrophage activates a T cell, which contacts a B cell that has surface receptors that bind to the type of antigen the macrophage presents
T cell releases cytokines that activate rapid replication of that B cell
B cells give rise to two types of cells:
plasma cells
primary immune response
polyclonal antibody response
memory cells
fewer released, usually dormant
secondary immune response

Antibodies
antibody molecule is built of several polypeptides, coded for by many genes
Y-shaped subuniT
constant regions provide antibody activity
variable regions are different in every antibody
specially shaped antigen-binding sites
antibody contorts to form a pocket around the antigen
we can produce
limitless
types of antibodies even though we have
limited
antibody genes
during early development of B cells, sections of their antibody genes move to other chromosomal locations, creating
new genetic instructions
for antibodies
every variable region consists of a V, J and D section

The Cellular Response: T Cells and Cytokines
immature T cells display diverse cell surface receptors
thymocytes that don’t attack self begin maturing, others die by apoptosis
helper-T cells: recognize foreign antigens on macrophages
different cell surfaces
cluster-of-differentiation (CD) antigens
some T cells can suppress an immune response that is no longer necessary
cytotoxic/killer T cells: attack virally infected and cancerous cells
link two surface peptides to form T cell receptors
perforin
destroys cells targeted by viruses before viruses can enter

Inherited Immune Deficiency
more than twenty inherited immune diseases
mutations in genes that encode cytokines or T cell receptors can impair cellular immunity, which targets cancer and viruses
abnormal cellular immunity causes malfunctioning humoral immunity
mutations in genes for antibody segments or that control B cell maturation impair immunity against bacterial infection
increase vulnerability to bacterial infection
severe combined immune deficiencies (SCIDs)
levels of severity

the body produces antibodies that attack the body’s own tissue
autoantibodies
5% of the human population has an autoimmune disorder
usually not inherited as single-gene diseases
dozens of genes are associated with multiple disorders

Lupus
produces antibodies that affect the connective tissues of many organs
affects several metabolic processes crucial to immune responses
variants of at least 10 genes can cause predisposition

Autoimmunity can arise in many ways:
Mother and Fetus
fetus and mother should recognize each other as nonself, but the immune system seems to have evolved away from attacking the other
T Regs
maternal immune system also produces T Regs
may be possible to stimulate production of T Regs
Scleroderma
discovery of Y chromosomes in cells from patients who are mothers to sons
mothers with scleroderma have more cell surfaces similar to their son’s cell surfaces than mothers without scleroderma
Rh Incompatibility
if an Rh+ woman conceives an Rh+ fetus with an Rh- man, the body will produce antibodies against the fetus
if there is a second Rh+ child, there can be enough antibodies to cause potentially fatal hemolytic disease in the fetus

Allergies
immune response to an allergen that does not actually pose a threat
cellular and humoral immunity
antibodies bind to mast cells
releases histamine and heparin
causes inflammation
activate helper T cells
genes clustered on chromosome 5q
IgE production on chromosomes 12q and 17q
mutations
filaggrin

Overview
a virus incorporates a host cell’s surface antigens into its own
cells that should have died in the thymus escape apoptosis
nonself antigen coincidentally resembles self
skewed X inactivation

Vaccines
an inactive or partial form of a pathogen
secondary immune response is activated
vaccines with entire bacteria or viruses can cause illness
super vaccine
new delivery method: genetically modified foods
herd immunity

Immunotherapy
amplifies or redirects the immune response
monoclonal antibodies boost humoral immunity
monoclonal antibody technology
cytokines boost cellular immunity
difficult to incorporate into drugs
interferons are used to treat cancer

Transplants
autograft
isograft
allograft
xenograft
rejection/acceptance:
immune system recognizes most tissues as nonself
launches immune response
physicians try to match HLAs or strip antigens from donor cells
immunosuppressant drugs
gene expression profiling
graft-versus-host disease

Ryan Bronson
Full transcript