Transcript Immunology Stack

Immunology Stack
Slackers Facts by Mike Ori
Disclaimer
The information represents my understanding only so errors and omissions are
probably rampant. It has not been vetted or reviewed by faculty. The source is our
class notes.
The document can mostly be used forward and backward. I tried to mark
questionable stuff with (?).
If you want it to look pretty, steal some crayons and go to town.
Finally…
If you’re a gunner, buck up and do your own work.
B and T Cell progenitor cell
Pre-lymphoid
HSC stem cell markers
CD34 (stem cell factor?), CD133
Myeloid progenitor descendents
Granulocytes (Neutrophils, monocytes,
Basophils, Eosinophiles)
Erythrocytes
Platelets
Myeloid Lineage Cytokines
IL-3, IL-5, GM-CSF
Lymphoid Lineage Cytokines
IL-3, IL-7
B Cell Markers
CD19, CD20
Plasma Cell Markers
CD38
Immature B Cell Ig
Early: Heavy chain + psuedo-light chain
Late: IgM with heavy and light chains
Mature B Cell Ig
IgM, IgD
Common T-Cell Marker
CD3
T Helper Markers
CD4
CD3 (all T’s)
Cytotoxic T Cell Marker
CD-8
CD-3 (all T’s)
B Cell Maturation Site
Bone marrow
T Cell maturation site
Thymus
Congenital lack of thymus, low T cell count, low
IgG (?)
DiGeorge syndrome
T cell receptor subunits
Alpha-beta on CD-4, CD-8
Gamma-delta (not discussed)
Isotype
The major class of an antibody (IgM, IgG, etc)
Allotype
Allelic type changes between Ig of the same
isotype.
Idiotope
Antigenic determinant associated with the
variable region.
Idiotype
Sum of all idiotopes
Anti-idiotype
The molecule that fits in the idiotype
Domain
A globular region on an antibody consisting of
100-110 amino acids
Hypervariable Region
The area of an antibody subject to
recombination and to somatic hypermutation
Complementarity determining region
Antigen
A compound recognizable by antibodies
Immunogen
An antigen capable of creating an immune
response
Epitope
The part of an antigen that an antibody
recognizes
Paratope
The portion of an antibody that binds the
antigen
Hapten
A small molecule that is able to cause an
immune response only when bound to a
carrier
Carrier
A molecule that can bind haptens in way that
can elicit an immune response
Heavy chain types
Chains are defined by the type of Ig created
(M,A, etc)
Light chain types
Kappa and lambda
Light chain rearrangement order
Kappa then lambda
Four chances
Heavy chain rearrangement order
Random. Either the maternal or paternal
rearranges. Two chances
Hinge region function
Contributes flexibility to the antibody. Protein
cleavage location.
Antibody Fab region function
Binds the antigen
Fc region funciton
Conveys the non-antigen binding properties of
the antibody
J chain function
Joins antibody monomers
Secretory protein function
Binds dimeric IgA at the cell surface allowing for
transcytosis
Monomeric Ig with complement binding region
IgG
Monomeric Ig without complement binding
region
IgE
Pentameric Ig
IgM
Dimeric Ig
IgA
Most abundant Ig in the body (total)
IgA
Most abundant Ig in the serum
IgG
IgG half life
23 days
Transplacental antibody
IgG
Affinity
The strength of interaction between a single
hapten or epitope and an antibody.
Avidity
The sum affinity of an antibody
Mucosal surface antibody
IgA
Ig of initial infection
IgM
Breast milk associated antibody
IgA
Principle light and heavy chain binding method
Disulfide bonds
Name the heavy chain variable segments
V–D–J
Name the light chain variable segments
V–J
Heavy chain reorganization scheme
D-J combine then V combines with VDJ
Light chain reorganization scheme
VJ recombine
Since there are only two regions, they combine
directly.
What is the function of recombination signal
sequence
Sit before and after each segment serving as
homology regions that assist in removal of
segments.
What is the function of recombinase activating
genes
Recombination proteins that excise regions
flanked by RSS regions.
What is combinatorial diversity
Antibody diversity generated by recombining V –
D – J segments
Junctional diversity
Diversity generated by repair of imprecise joins
as a result of RSS excision
What is somatic hypermutation
Introduction of point mutations during B cell
clone development
IgM -> IgE class switching cytokine
IL-4
IgM to IgG class switching cytokine
Interferon ??
Cell causing class switching
CD4 T Helper
Name the complement pathways
Alternative
Classical
Lectin
Complement functions?
Opsonization and neutrophil/macrophage
activation (C3b)
Lysis (MAC)
Activation of mast cells (C3a/C5a)
Chemotaxis (C5a > C3a)
B cell function
When activated, become antibody secreting
plasma cells
CD4+ T cell function
Create cytokines that activate other immune
system components. Can have some direct
antimicrobial effects
CD-8 T cell function
Destroy host cells displaying antigens on MHC-I.
Secrete pore forming and proteolytic enzymes
under influence of IFN-gamma (and TNFalpha?)
T Regulatory cell marker
CD 4
T Regulatory cell function
Regulate the action of the immune system to
prevent autoimmunity
CD4 TH cell classes
TH1 – Viral association
TH2 – allergy/parasite association
TH17 – autoimmune association
MCH used to display intracellularly derived
protein fragments
MHC-I
MHC used to display extracellularly derived
protein fragments
MHC-II
Proteasome function
Degrades intracellularly derived peptides
TAP function
Passes proteasome processed proteins into the
ER for display by MHC-I molecules.
MHC-I structure
MHC-II structure
MHC-I peptide fit
Fits peptides up to 10 amino acids in length.
Has closed ends. Peptides interact with
pockets that determine the fit.
MHC-II peptide fit
Fits peptides up to 20 amino acids in length.
Has open ends. Peptides interact with pockets
that determine the fit
MHC-II presenting cells
Dendritic cells
Macrophages
B cells
Thymic epithelial cells
MHC-I presenting cells
All cells
CD-28 to CD-80/86 function
Signals interaction of TCR with MHC is occurring
with an APC. This activates the cell.
CD-28 to CTLA-4 interaction
Signals interaction of TCR with MHC is occurring
with a non APC cell. This sparks anergy.
Adjuvant
A substance which when mixed with an
immunogen improves the immune response
to the immunogen
MHC inheritance
Usually inherited as haplotypes due to
chromosomal colocation and proximity.
Hence 50% homology(word?) with each
parent.
MHC Expression
Codominant expression with both parental
haplotypes
MHC-I Gene nomenclature and quantity
A,B,C genes
MHC-II Gene nomenclature and quantity
Three pairs of alpha and beta genes. DP, DQ, DR.
T cell signal 1
MHC-II interaction with APC stimulating T cell
activity
T Cell signal 2
Co-stimulation of T cell by B7 (apc) and CD28 (T
cell) that stimulates T cell activity
T cell signal 3
Signals by cytokines from presenting or adjacent
APC that stimulate T cell activity
Immunologic synapse
TCR, CD4/8, and co-stimulatory molecule
clusters at the point of contact between APC
and T cell.
Perforin function
CD8 T cell product that forms pores in plasma
membranes.
Granzyme function
Proetolytic enzymes released from CD8 cells
TH1 cytokines
IL-2
IFN-gamma
TH2 Cytokines
IL-4,5,6,10
TH17 cytokines
IL-17,23
Treg cytokines
CTLA-4
IL-10
Type I hypersensitivity characteristic
Antigen IgE interaction
Type II hypersensitivity characteristic
Antibody complexes form on cell surface
antigens. Complement fixation/opsonization
results in cell death.
Type III hypersensitivity characteristics
Circulating antibody/antigen complexes deposit
in kidney glomeruli, eyes, synovium of joints,
choroid plexus, skin
Type IV hypersensitivity characteristics
TH1 mediated activation of macrophages in
response to self or modified self antigens
presented by tissue macrophages
Type I Hypersensitivity Examples
Allergic rhinitis
Allergic asthma
Urticaria
Eczema
Systemic anaphylaxis
Type II hypersensitivity examples
Goodpasture’s syndrome
Transfusion reactions
Erythroblastosis fetalis
Autoimmune hemolytic anemia
Rheumatic fever
Hyperacute graft rejection
Type III hypersensitivity examples
SLE
Arthus Reaction
Serum sickness
Rheumatoid arthritis
Farmers lung
Type IV hypersensitivity types/examples
Contact hypersensitivity
Tuberculin hypersensitivity
Granulomatous hypersensitivity
Jones Mote Hypersensitivity
Cutaneous basophil activation
Jones-mote type IV hypersensitivity
Reddening, edema, necrosis following repeated
intradermal injections at a site
Arthus reaction
Molecular Mimicry
When a portion of a protein from an infectious
agent mimics a self protein such that cross
reactions can occur
What cell type is thought to control
autoimmunity
T-reg (CD4 subset) cells
What cells are thought to play a role in
developing autoimmunity
TH17 CD4 cells
Estrogen’s role in autoimmunity
Induces IFN-gamma and can push TH2
responses to TH1 responses leading to TH1
mediated diseases like MS
B Cell defect sequelae
Recurrent pneumonia, sinusitis, septicemia
T Cell defect sequelae
B cell defect
Wide ranging opportunistic infection with
viruses, bacteria, protozoa
Think about AIDS related disease
Neutrophil defect sequelae
Recurrent oral ulceration
Recurrent fever
Recurrent bacteremia
Complement defect <=C3/C4
Recurrent pyogenic infection
Autoimmune disease
Complement defect >= C5
Recurrent Neisserial infection
Complement C9 defect
No known disease
Low T cell count due to congenital absence of
thymus
DiGeorge Syndrome
Cr22 deletion
Defective gamma chain for IL-2 receptor
X-linked SCID due to defective intracellular
signaling
Adenosine deaminase deficiency
SCID due to enzymatic defect
Absence of T and B cells
Sever combined immunodeficiency
Deficiency causing frequent pyogenic infections
such as pneumonia with low Ig
Lack of B cell activity
Deficiency causing frequent viral or intracellular
bacterial infection
T cell deficiency
Hyper IgM cause
Defect in T cell class switch signaling to B cells.
Can result from T cell or B cell defects in
CD40L/CD40, IL-4/Receptor, IL-2/Receptor
Histamine effects
Bronchial constriction
Vasodilation
Increased mucous secretion
Pemphigus vulgaris detail
Type II hypersensitivity that attacks
desmosomes in the epidermis resulting in
blistering, scaling, and separation of the layers
of the epidermis.
Bullous pemphigoid details
Type II hypersensitivity reaction against
hemidesmosomes in the dermal/epidermal
junction resulting in blistering.
B=between layers
Hemolytic anemia hypersensitivity details
Type II reaction by preformed isohemagglutinins
in the blood directed against A,B, Rh blood
groups
Type II hypersensitivity immune complex
deposition characteristics
Smooth, ribbon-like deposition of Ab in the
glomerulus or other structures as a result of
binding cellular Ag present in the structure
Type III hypersensitivity immune complex
deposition characteristics
Lumpy deposition of immune complexes in the
glomerulus due to deposition of preformed
Ab/Ag complexes
Hypotension, rapid heart rate, bronchiole
constriction, laryngeal obstruction, pulmonary
edema is a sign of what?
Anaphylaxis
Anaphylaxis mechanism
Antigens reach the blood stream and activate
basophils by interacting with IgE bound to
their surface. This results in massive
histamine release as a consequence of
degranulation.
Type IV skin test positive sign
Induration
What is a forward blood cell typing test
Mixture of pt RBC with known anti-sera to
directly read the pt blood type
What is a reverse blood cell typing test
Addition of pt sera to known A,B,O,Rh blood
cells. Yields the Ab’s the patient has. Can
infer the PT type.
InfeR=Reverse
What is the purpose of a direct antiglobulin test
AKA Coombs test
Detects antibodies already directly bound to PT
RBC’s. Can confirm reason for hemolysis
Wash cells
Add anti-human IgG
Observe clumping
What is the purpose of the indirect antiglobulin
test
Detects antibodies in the patient serum. Used
in prescreening to prevent hemolytic reaction
Add serum to antigenic RBC
Incubate and wash
Add anti-human IgG
Observe clumping
Autograft definition
Transplant of one’s own tissues to a new site in
the body. CABG donation from leg veins.
Isograft defintion
Transplant of tissue from a genetically identical
individual. In mice this occurs in highly inbred
strains. In humans it can only occur in
monozygotic (identical) twins.
Allograft definiton
Transplantation of tissue between genetically
distinct members of the same species
Xenograft definition
Transplant of tissue between members of
different species.
Histocompatibility
Sharing histocompatibility markers.
Graft vs Host Disease (GVHD) defintion/cause
T cells in a graft react against host tissue to
cause disease. Usually thought of in the
context of stem cell transplant but may also
occur in other types of transplants.
What is the major rejection mediator cell
CD4 T Helpers
Rank the MHC classes in order of rejection
importance
MHC-II – most important
MHC-I – least important
NOTE: ABO Rh are the most important overall
Hyperacute graft rejection characteristics
Occurs within minutes of establishing blood flow
to a transplanted organ as a result of
isohemagglutinins interaction with blood type
antigens on the surface of endothelial tissue.
Cannot be stopped.
Accelerated graft rejection characteristics
Rejection beginning within 2-5 days post
transplant as a result of prior sensitization to
antigens on donor cells. Spin up of previous
memory cells. Generally cannot be stopped.
Acute graft rejection characteristics
Rejection beginning 7-21 days post transplant as
a result of HLA mismatch induced activation of
T cells. Generally can be suppressed by
interfering with T cell function. Usually
involves skin, GI tract, liver but not connective
tissue.
Chronic graft rejection characteristics
Graft rejection after 3 months due to disruption
of graft tolerance. Generally cannot be
reversed. Typically involves skin, GI tract, liver,
and connective tissue.
Cyclosporin effects
Suppressed production of IL-2 by T helpers
GVHD symptoms
Early: diarrhea, jaundice, rash, platelet
consumption
Late: Anorexia, scaly rash, dry mouth, dry eyes,
liver dysfunction