Slackers Facts by Mike Ori

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