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immunology
study of physiological mechanisms of humans used to defend body from invasion by microorganisms
CD4 T cells are MHC-II restricted and helpers, CD8 T cells are MHC-I restricted and cytotoxic
compare CD4 T cells with CD8 T cells
immunity
Resistance to disease
innate immunity
nonspecific, can be inducible or non-inducible, natural barriers and the inflammatory response (phagocytosis, inflammation, complement proteins)
1st is external, like skin and mucosa.
2nd is internal, including WBCs and inflammation.
3rd is adaptive responses, and having the memory to recall a pathogen the body has seen before
differentiate bw the 1st, 2nd, and 3rd (acquired) lines of defense
Specificity of Immune Response
Involves recognition, activation and response
may be natural (innate) or acquired (adaptive)
Memory immune response
recognizes and mounts even stronger attacks on previously encountered pathogens
Recognition (immune response)
sense of self and non-self (ability to know body's natural microbiome vs pathogens, failure in this aids in autoimmune disease)
adaptive immunity
the ability to recognize and remember specific antigens and mount an attack on them (either humoral or cell mediated)
Humoral mediated immunity (HMI)
main defense against extracellular pathogens
cell mediated immunity (CMI)
main defense against intracellular pathogens, usually direct cell-to-cell contact or production of cytokines
monocyte
3-10% of WBCs in periph blood, give rise to macrophages, agranulocytes
macrophage
large phagocyte found in lymph nodes and other tissues of the body
ex: Kupffer cells (liver), alveolar, microglial; die by apoptosis
granulocyte
a white blood cell that contains multiple small granules in its cytoplasm
neutrophil
40-75% of WBCs in periph blood, granulocytic and phagocytic leukocyte formed in bone marrow. aka PMNs
eosinophil
white blood cell containing granules that stain red; associated with allergic reactions
NK cell
3% of periph WBCs, large and granular, mediate rapid lysis of virus-infected, tumor, and foreign graft cellcells
chemotaxis
movement by a cell or organism in reaction to a chemical stimulus
opsonin
an antibody or other substance that binds to foreign microorganisms or cells, making them more susceptible to phagocytosis.
defensin
A type of protein made by phagocytes that kills bacteria and enveloped viruses by insertion into their plasma membranes.
oxidative burst
oxygen-dependent, reactive oxygen molecules (O2-, H2O2, OH-) increase during phagocytosis to better enable phagocytes
hygeine hypothesis
suggests that limiting exposure to pathogens may lower immune tolerance and the ability to cope with harmless antigens
Pattern Recognition Receptors (PRRs)
cell proteins able to recognize specific molecular patterns
Toll-like receptors (TLRs)
-A type of PRR
-Recognize PAMPs
-Set in motion a cascade of events inside the cell that amplifies and orchestrates a defense response to the pathogen
mast cells
present in connective tissue (esp blood vessels and nerves), promote inflammation, granules w heparin and histamine. associated w type 1 (IgE) hypersensitivity rxns (allergic)
Extravasation
interactions bw PMNs and endothelial cells (selectins, integrins). also transendothelial migration aka diapedesis
oxygen-independent killing
defensins, proteases, hydrolases
heat, pain, swelling, redness
4 cardinal signs of inflammation
C-reactive protein (CRP)
member of pentraxin family. early indicator of acute inflammation, but nonspecific. can detect within 6-12 hours after injury.
elevated in autoimmune disease, transplant rejection, malignant disease, heart attack
erythrocyte sedimentation rate (ESR)
a nonspecific blood test to measure how quickly erythrocytes settle at the bottom of a test tube containing a blood sample - measure of inflammation
the most important, aka the heart of all 3 pathways
C3 in the complement cascade
C5b6789
what's the alphanumerical code for the membrane attack complex?
complement fixation
uses virus-specific antigen, and reaction between antibody and antigen cause fixation of the complement, resulting in membrane lysis
increasing vasodilation and permeability
C2b, C3a, and C5a are known for
chemotaxis (neutrophils and monocytes)
C5a alone is known for
anaphylaxis (inflammation, degranulating mast cells and basophils)
C3a, C4a, C5a are known for
Ab-Ag complexes OR crp
what is the classical pathway activated by?
C1, C2, C4
what are the unique components of the classical pathway
2 IgG or 1 IgM
what does the classical pathway require in terms of recognition
contact w foreign substance, not Ab dependent (diff from classical)
what is the alternative pathway activated by?
Factor B, Factor D, Properdin
what are the unique components of the alternative pathway
IgA dimer binds to antigen, allowing for a quicker response than classical
what does the alternative pathway require in terms of recognition
Zymogen
protein secreted in an inactive form and activated by cleavage
feed-forward mechanism of complement activation, where C3 is fed back and forth bw classical and alternative bc both need C3b
explain the amplification loop
independent of antibody, instead lectin binds to mannose-containing carbs of bacteria, fungi, protozoa, viruses. interact with two proteases and make MASPs
explain the MBL pathway
immunogen (remember, all immunogens are antigens)
substance capable of producing immune response
antigen
substance that has ability to interact with BCR, TCR, or Ab
hapten
elicits immune response only when attached to a carrier (too small to be immunogenic alone)
epitope
an antigenic determinant; the particular chemical group or groups in a macromolecule (antigen) to which a given antibody binds.
agretope
region of processed Ag that binds to MHC molecule
valence
# of epitopes / molecule
antigenicity
capacity of Ag or hapten to bind to Ab, TCR, or BCR, specific reactivity!!!
immunogenicity
inherent ability of a substance (immunogen) to stimulate immune response, form antibodies, and activate lymphocytes (like T cells)
heterologous antigens
related antigens from another species
paratope
antigen binding site on the antibody
antibody (immunoglobulin)
protein produced by B cells that protects against substances that are potentially harmful to the body
allotype
the types of antibodies found within one species
idiotype
the types of antibodies found within one individual
isotype
The types of antibodies found in all different individuals in related species
hybridoma
a cell hybrid produced by the fusion of Bcells (plasma) with myeloma cells
electrophoretic separation
many Abs are isolated in gamma globulin part of the serum during what process
4 polypeptide chains in shape of Y
what does the monomer structure of immunoglobulin look like
IgG antibodies
- 75% of serum Ab
- activates complement (Ig__3 is more effective than 2, than 1.. 4 doesn't activate
-C1q MUST CROSSLINK 2 or more of these
- crosses placenta at birth (moms give high levels to babies)
- neutralizes pathogens so no longer infectious
IgM antibodies
- 5-10% of serum Ab
- pentamer (i.e. 10 binding sites)
- v large, so confined to intravascular spaces
- first antibody produced after antigenic exposure
IgA antibodies
- 10-15% of total serum Ab
- the predominant antibody in secretions (tears, milk, intestinal/genital fluids)
- secretory component: tethers it to mucus and protects against proteolytic enzymes
IgD antibodies
- 0.2% of serum Ab
- found on surface of B lymphocytes as BCRs
- functions in activation of B cells
IgE antibodies
- trace amts in serum Ab
- mast cells, basophils, activated eosinophils all have high affinity receptors for this
- potent activator of allergic reactions
noncovalent
what kind of bonds form between Ags and Abs?
hydrogen bonds
noncovalent attraction bw hydrogen and electronegative N O or F
electrostatic forces
opposite charges attract, like Na+ and Cl-
van der Waals forces
(+) or (-) charged regions of a polar molecule attract each other
hydrophobic bonds
association of hydrophobic groups
affinity
strength of a single Ag-Ab interaction, determined by sum of noncovalent attractive forces
avidity
strength with which a multivalent Ab binds to a multivalent Ag
avidity, affinity
IgM has a greater ______ than IgG, but IgG has a greater ______ than IgM
monoclonal antibodies (mAbs)
identical laboratory-made antibodies produced by plasma cell clones
major histocompatibility complex (MHC)
Group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances.
MHC restriction
the property that a given T-cell receptor recognizes its peptide antigen only when the peptide is bound to a particular form of MHC molecule.
cytokine
small proteins/peptides secreted by cells that act to change the behavior of other cells, bind to specific receptors on target cells
interleukin
- A chemical secreted by a T cell (usually the helper Ts) that stimulates activation and proliferation of other immune system cells.
- basically secreted by WBCs to stimulate other WBCs
interferon
Protein produced by cells in response to being infected by a virus; helps other cells resist the virus by interfering with viral replication
monokine
a cytokine released by a monocyte (macrophage).
lymphokine
a cytokine released by a lymphocyte.
anergy
absence of the normal immune response to a particular antigen or allergen
human leukocyte antigen (HLA)
aka MHC for humans, genes that code for proteins found on cell surfaces that help immune system recognize foreign substances
anamnestic response
upon second encounter with same pathogen immune system mounts a faster and more intense response
recovery from infection
give an example of natural active immunity
vaccine
give an example of artificial active immunity
IgG in placenta, IgA in breast milk
give an example of natural passive immunity
IVIG
give an example of artificial passive immunity
bone marrow and thymus
what are the main primary lymphoid tissues
lymph nodes and spleen
what are the main secondary lymphoid tissues
originate in the bone marrow, head to spleen for maturation where they go thru somatic recombination to determine specificity, then mature b cells go to blood stream then lymph nodes, then to another secondary tissue
explain the cycle of B cells (where they originate, where they go, how they mature, etc)
originate in the bone marrow, travel to the thymus for maturation and become T cell receptors, enter blood ad go to lymph notes, then other secondary tissues
explain the cycle of T cells (where they originate, where they go, how they mature, etc)
b cells have a chance to alter themselves, t cells don't
what's the difference between how B and T cells mature, other than the location?
MALT (mucosa-associated lymphoid tissue)
- the collection of lymphoid tissues that protect the epithelia of the digestive, respiratory, urinary, and reproductive systems
- similar to lymph node, just not encapsulated
Gut-associated lymphoid tissue (GALT)
- A collection of lymphoid tissue in the gastrointestinal tract that includes the appendix, the lacteals, and Peyer's patches.
M cells
members of GALT, filter and funnel antigens into lymphoid tissues
somatic recombination
how do b cells determine their specificity
MHC-I
- on all nucleated genes, bind antigens synthesized within cells (intracellular, endogenous!!!)
- present antigens to CD8+, cytotoxic T cells, and NK cells