Immunology Flashcards
myeloid lineage
Mast cells. Granulocytes (neutrophils, basophils, eosinophils). Dendritic cells. Monocytes. Macrophages.
lymphoid lineage
T/B lymphocytes.
NK cells.
innate immunity (general)
No memory.
First line of defense.
Broadly specific.
Not antigen specific.
innate immunity: mechanisms
Phagocytosis of bacteria by neutrophils and macrophages.
Cellular cytotoxicity: NK cells destroy virus infected/cancerous cells.
Inflammation: mast cells (tissue) and basophils (blood) degranulate against parasite infections.
Chemokine attraction: release TNF/IL-1, inducing adhesion factor expression so WBCs can migrate into tissues.
Microbe recognition: dendritic cells, neutrophils, macrophages express PRRs.
PRR
Pattern Recognition Receptor.
Recognize common features broadly specific to a group of pathogens.
Binds to PAMPs.
PAMPs
Pathogen Associated Molecular Patterns.
Pathogen-specific.
Recognized by PRRs.
Adaptive Immunity
Antigen specific response.
By B cell and T cells.
Produce memory response.
clonal expansion
Initiated by antigen binding.
B cell divides into memory B cells (express surface antibody) and plasma effector cells (secrete antibody).
T cell divides into helper T cells (CD4+, produce cytokines) and T-cytotoxic cells (CD8+, kill infected cells).
plasma effector cells
secrete antibody.
Made after B cell comes into contact with antigen.
humoral immunity
B-cell mediated response to EXTRACELLULAR pathogens.
cell-mediated immunity
T-cell mediated response to pathogen infected cells/tumor cells.
helper T cells
CD4+
produce cytokines
T-cytotoxic cells
CD8+
kill infected cells
antigens
Usually protein, carbohydrates.
Not usually lipids, nucleic acid (NOTE: Lupus: anti-DNA Ab)
hapten
Non-immunogenic small molecule which can be made immunogenic by coupling to a protein.
primary lymphoid organs
Bone marrow: B cells.
Thymus: T cells.
Site of lymphocyte differentiation into mature naive cells.
secondary lymphoid organs
Site where naive lymphocytes encounter antigens.
Traps antigens and facilitates contact with immune cells.
Spleen.
Lymph nodes.
MALT.
Appendix.
Peyer’s Patches.
antibody (immunoglobulin) structure
2 identical H chains, 2 identical L chains.
Chains connected by disulfide bridges to form an antibody monomer.
2 binding sites for specific epitope.
Hinge region: flexible central H chain region (papain digests).
Fab region: L chain + top of H chain; forms antigen binding site at variable region (N-terminal) interface.
Fc region: Bottom of H chains, determines antibody effector function once bound to antigen.
immuloglobulin isotypes
IgM (pentameric + 1 J chain) IgD IgG (1-4) IgA (1, 2) (monomeric or dimeric) IgE
L-chain isotypes
Kappa 60%
Lambda 40%
mutliple myeloma
Neoplastic plasma cell condition.
Creates high concentration of MONOCLONAL antibody in blood.
Very large serum gamma-globulin peak with all either kappa or lambda.
primary response
1st antigen enounter causing clonal expansion (lag phase).
Mostly IgM pentamers secreted in serum.
memory response
Response to previously encountered Ag.
Shorter lag phase.
Higher Ab titer.
Class switching, SHM, selection occur.
BCR
B Cell Antigen Receptor.
Membrane bound Ig with signaling molecules Ig alpha and Ig beta.
neutralization
IgG and IgA bind toxin, virus, or microbe to inactivate pathogenic mechanism.
opsonization
IgG coats BACTERIA to promote phagocytosis by macrophages/neutrophils carrying Fc receptors (Fc{gamma}R).
ADCC
Antibody-Dependent Cell-mediated Cytotoxicity.
NK cells express Fc{gamma}Rs IgG bounf to viral antigens on infected cells or tumor antigens.
mast cell degradation
Mast cells express Fc{gamma}Rs recognizing IgE bound to parasitic antigens causing histamine release and inflammation to recruit eosinophils.
Note: Fc{gamma}Rs complex with IgE BEFORE IgE binds to antigen, which crosslinks 2 IgEs.
complement
Innate immune serum proteins that amplify inflammatory response.
Chemotactic factors direct phagocytic migration while other complement proteins porate bacteria.
IgG and IgM activate the complement system.
IgM
Fx: Complement system, mature naive B cell receptors.
Location: pentamer in blood, monomer in naive B cell membrane and tissues by diffusing out of capillaries.
IgD
Fx: mature naive B-cell receptors
Location: naive B cell membrane
IgG
Fx: complement system, neurtralization, ADCC, memory Bcell receptors
Location: blood, crosses placenta to fetus, memory B cell membrane
IgA
Fx: neutralization, memory B cell receptors
Location: secretory IgA dimers in mucosal surface, IgA monomers in blood/milk/saliva/tears
IgE
Fx: Mast cell degranulation, memory B cell receptors
Location: mast cell membrane (submucosal tissues), memory b cell membrane
light chain rearrangement: B lymphocytes
Encoded by V (variable), J (joining), and C (constant) regions.
Expresses either kappa or lambda.
Requires RAG-1 and RAG-2 (expressed only in lymphocytes)
loss of RAG-1 or RAG-2
loss of all lymphoytes.
Cannot due VDJ recombination
heavy chain rearrangement: B lymphocytes
Includes D (diversity) segments too. V-D-J-C. Two DNA rearrangements necessary to form VDJ region. C region encodes type of heavy chain (mu, delta, gamma, alpha, epsilon).
class switch
After activation of B cell by antigen.
Moves VDJ in front of a new constant region.
Requires AID (activation-induced cytidine deaminase).
Allows for change of constant region between isotypes (i.e. from IgM to IgG).
Occurs in germinal center of secondary lymphoid organs.
After class switch, B-cell can only produce ONE type of antibody class (not IgM and IgD like mature B cells
antibody diversity
1) class switch
2) germline: multiple VDJ segments, two sets from parents
3) combinatorial: all possible combinations of VDJ genes and heavy/light combos
4) junctional: imprecise joining of VDJ segments by exonucleases and TdT
junctional diversity
imprecise joining of VDJ segments.
Exonucleases randomly remove nucleotides from joining segments.
TdT (Terminal Deoxynucleotidyl Transferase) randomly adds nucleotides to ends of segments prior to joining.
somatic hypermutation
Random point mutations in variable region DNA occurring during B cell clonal expansion during memory response.
Creates antibodies with increased affinity for antigen.
clonal selection
The destruction of B cells expressing mutated antibodies with decreased antigen specificity or affinity.
Survival of the fittest in secondary lymphoid organs.
hyper-IgM syndrome
loss of AID (activation-induced cytidine deaminase)
Pre-B cell
Undergone heavy chain VDJ recombination.
No light chain.
Immature B cell
Undergone light chain VDJ recombination.
Complete IgM.
Negative selection occurs at this stage.
negative selection
cells expressing autoreactive IgM are removed at this stage.
In bone marrow.
Mature B cell
Express both membrane IgM and IgD by alternative splicing.
Are naive.
Migrate to secondary lymphoid tissues to encounter antigen.
Become plasma cell and memory B cell.
antisera injections
passive immunization with IVIG (intravenous Ig) pooled from donors.
Polyclonal.
Half-life: 3 weeks.
natural passive immunity
Maternal IgG crosses placenta to fetus.
sIgA in milk, lines gut mucosa.
M(abs)
Monoclonal antibody raised to a specific epitope.
Via hybridomas.
chimeric M(abs)
Mouse M(ab). Has mouse variable regions. Human constant region.
humanized M(abs)
Onlyl Ag binding pocket and CDRs remain from mouse M(abs).
combinatorial libraries
fully human sequence from B cell gene library.
ELISA
Enzyme Linked Immunosorbent Assay.
Antibody-enzyme coupling detects substances.
Ex: hCG detected by home pregnancy test, binding activates enzyme.
Immunohistochemistry/ Flow Cytometry
Binding to fluorescent-linked antibody
antigen presenting cells (APCs)
Dendritic cells, macrophages, monocytes, B cells.
Capture antigens using TLRs that recognize PAMPS for presentation to T cells.
TLR binding
Causes APCs to produce cytokines.
Causes maturation of APC, losing adhesiveness, travels to lymphatic system.
Present antigen to lymph node localized T cells.
IL-1 + TNF
1) Induce endothelial chemokine production and endothelial adhesiveness, causing lymphocytes to attach and transendothelially migrate to site of infection, causing inflammation (phagocyte accumulation at APCs).
2) cause hepatic release of acute phase proteins like CRP (indicates illness, acts on hypothalamus to produce fever, depression, anorexia).
IFN-alpha, IFN-beta
antiviral cytokines
chemokines
chemotactic or attractant cues to draw lymphocytes to APC.
IL-12
Activates TH1 cells and NK cells.
Activates production of IFN-gamma by T cells and NK cells.
IL-10
inhibitory cytokine
MHC/HLA
Major histocompatibility complex.
Human Leukocyte Antigen.
Presents Ag allowing TCR to recognize it.
Peptide fragments from phagocytosed microbes in external groove/cleft.
Determines transplant/graft rejection.
MHC/HLA genes: class I
A, B, C genes.
Encoded on p arm of chromosome 6.
Linked and inherited by haplotypes.
MHC/HLA genes: class II
DP, DQ, DR genes.
Encoded on p arm of chromosome 6.
Linked and inherited by haplotypes.
HLA gene polymorphism
Alleles associated with ethnic background.
Maternal/paternal haplotypes (1/4 chance of HLA match in siblings).
Variation exists in antigen presenting groove.
MHC class I
Polymorphic, transmembrane alpha chain encoded by A, B, C genes.
Non-polymorphic B2-microglobulin (encoded by unlinked gene.
Expressed on surface of ALL nucleated cells.
MHC class II
Polymorphic, transmembrane alpha-chain and beta chain.
Encoded by DP, DQ, DR genes.
Expressed ONLY on antigen presenting cells and activated T cells.
ankylosing spondylitis
HLA allele association: B27
narcolepsy
HLA allele association: DR2, DQ1
Type I Diabetes
HLA allele association: DR3, DR4
Rheumatoid arthritis
HLA allele association: DR4
Bare lymphocyte syndrome
failure to express MHC molecules
