Immnunology

Fas-fas ligand

type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis and its interactions with its receptor plays an important role in the regulation of the immune system and the progression of cancer.

enterobacterial LPS

uses TLR4

Mannose binding lectin complex pathway

Mannose binding lectin (c1q like.) MBL is associated with serine protease (C1r and C1s like); MLK-MASP binds polysaccharides on gram neg bacteria, and initiates classical pathway activation independent of Ab. MASP cleaves C4 and C2

Toxic oxygen-derived products

Mechanism of bacterial killing; superoxide O2-, hydrogen peroxide H2O2, singlet oxygen, hydroxyl radical OH

fab (fragment antigen binding) region

variable region of antibody that binds antigen. composed of one constant and one variable domain of heavy and light chains. the variable domain contains the paratope

MHC

very polymorhic (occur in dif forms). MHC locus= human leukocyte antigen (HLA) on the short arm off chromosome 6; also polygenic- each gene encodes dif type of molecule with a range of peptide binding specifications. have a broad range of binding. they have co dominant expression (big deal when it comes to transplant matching

Timing is everything

virus infects host--> inf-a, inf-b--> induces resistance to viral rep in all cells--> increases MHC class I expression and antigen presentation in all cells--> activates dendritic cells and macrophages--> activates NK cells to kill virus infected cells

carrier proteins and adjvuncts

ways to improve immune response to immunogens

IgG2

Occurrence (% of total IgG)- 2- Half-life-23 Complement binding- + Placental passage- +/- Binding of monocytes-+

IgG4

Occurrence (% of total IgG)- 3 Half-life- 23 Complement binding- --- Placental passage- ++ Binding of monocytes- +/-

IgG3

Occurrence (% of total IgG)- 7 Half-life- 7 Complement binding- +++ Placental passage- ++ Binding of monocytes+++ (long disulfide bond chain)

IgG1

Occurrence (% of total IgG)- 70 Half-life-23 Complement binding- + Placental passage- ++ Binding of monocytes- +++

foreignness, molecular weight (at least 1000Da), degradability, chemical complexity

what evokes an immune response

cytokines

what links innate and adaptive responses

CD59 (protectin) also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin***

widely expressed on membranes. attaches to host cells via a glycophosphatidylinositol (GPI) anchor. When complement activation leads to deposition of C5b678 on host cells, this can prevent C9 from polymerizing and forming the complement membrane attack complex.It may also signal the cell to perform active measures such as endocytosis Mutations affecting GPI that reduce expression of this protein and decay-accelerating factor on red blood cells result in paroxysmal nocturnal hemoglobinuria Viruses such as HIV, human cytomegalovirus and vaccinia incorporate this host cell protein into their own viral envelope to prevent lysis by complement.

CR3

without it, you have impairment of phagocytosis specificity- c3bi function- stimulates phagocytosis cell types- macrophages, monocytes, polymorphonulcear leukocytes, FDC

t cell dependent b cell activation

T cell talks to a B cell about an antigen (t cell binds to MHC), they shake hands and give each other stimulations (co-stimulation)- this also stimulates class switching and the B cell becomes excited and divides. some will become plasma cells that secrete antibody and others memory cells. Class switching IgG- IFNgamma IgE- IL4, IL13 IgA- IL5 note- one antigen specific T cell can initiate differentiation for multiple B cells within dif antibody specifications

dendritic cells

TNF-alpha stimulates migration to lymph nodes and maturation--> initiation of adaptive immune response

RAG 1 and 2

The immune system generates diversity of antibodies by shuffling, cutting and recombining a few hundred genes (the VDJ genes) to create millions of permutations, in a process called V(D)J recombination. RAG-1 and RAG-2 are proteins at the ends of VDJ genes that separate, shuffle, and rejoin the VDJ genes. This shuffling takes place inside B cells and T cells during their maturation.They bind to RSS motifs, make a nick in ds DNA and bring together gene segments to be recombined. If RAG 1 and 2 are deficient- end up with sever combined immunodeficiency (SCID) bc you cant create any mature immune cells

Ig variable and hypervariable regions

V regions are unique to each antibody; 3 hypervariable (HV) regions in L and H chains. regions between HV are framework regions (FR). FR form beta seats, and HV are on the outer edges of barrel. total of 6 HV loops on the H and L chains together= complementarily determining region. the combination of H and L chain HV regions determines the final antigen specificity

genes coding for TCR

VDJ genes are mixed together in a more complicated manner than immunoglobulin genes. alpha and gamma (y) for V and J regions. beta and delta for VDJ segments. also uses RAG. if rag is missing (SCID)

passive immunity

a form of immunity to an antigen that is established in one individual by transfer of antibodies or lymphocytes from another individual known to be immune to that antigen. i.e.- mum to baby antibody transfer

Antibody-dependent cell-mediated cytotoxicity (ADCC)

a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies. It is one of the mechanisms through which antibodies, as part of the humoral immune response, can act to limit and contain infection. another method for NK cells to kill antibody binds to antigen. this is recognized by a natural killer cell, which then lyses the pathogen

dendritic cells

abundant interfaces between the external and internal environments; continuously sample surroundings by endocytic processes and can become higly motile, migrate to draining lymph nodes upon activation. Good at T cell activation

IgA

abundant on mucosal surfaces as a first line of defense. bactericidal for gram - organisms in the presence of lysozyme. efficient viral agglutinator preventing viral attachment to epithelial cell viral receptors and plays a role in passive immunotherapy. can be transferred from mom to child in breast milk. has a long hinge region and a nice secretory component. 2 subclasses (A1 and A2) found in mucosal secretions. they have dif hing regions and disulfide bonds usually dimeric, mucosal surfaces, lousy at fixing complement, antiviral and antibacterial

th1 and Th2

activate macrophages, killer T cells, B cells and secretes IFN- gamma, IL-2, and TNF alpha TH2-activates eosinophils, mast cells, basophils and secreted IL-4, IL5, IL13

IL-12

activates NK cells and induces the differentiation of CD4 cells to TH1 cells

TNF-alpha

activates vascular endothelium and increases vascular perm which leads to increased entry of igG, complement, and cells to tissues and increased fluid drainage to lymph nodes. systemically leads to fever and mobilization of metabolites, and shock

IL-1 beta

activates vascular endothelium, lymphocytes, local cell destruction, and increases access of effector cells. systemically leads to fever and production of IL-6

liver

acute phase proteins (C-reactive protein, mannonose binding lectin) --> activates complement opsonization

chronic granulomatous disease clinical manifestations

affected males with infections in the first year, pneumonia, lmymphadenitis, abscesses in skin/viscera . X linked

IgG biological properties

agglutination and precipitation, placental passage (G1, G3, G4), opsonization , antibody dependent cell mediated cytotoxicity (G1 G3); Complement activation (G1,G2, G3); toxin and viral neutralization (when Ig prevents bacterial adherence), and bacterial immobilization

antibody(Ab)

aka immunoglobin. Y shaped protein produced by plasma cell and is used in the immune system to neutralize pathogens. it recognizes an antigen via fab's variable region. each antibody contains a paratope that is specific for an epitope on an antigen. using this binding mechanism an antibody can tag a microbe for attack by other parts of the immune system. communication with other components of the immune system is mediated by the fc region (at the base of the y).

Ig Allotypes

allele of the antibody chains found in a person. these exist in Ig constant regions. co-dominant autosomal mendelian genes, allotypic variants of gamma, alpha, and L chains; these are used forensically, and it may confer biological advantage for some infectious agents. bc of these-people tend to respond to infections differently

ADCC

an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies.requires an effector cell which classically is known to be natural killer (NK) cells that typically interact with IgG antibodies.However, macrophages, neutrophils and eosinophils can also mediate ADCC, such as eosinophils killing certain parasitic worms known as helminths via IgE antibodies

paratope

analogous to a lock and is specific to one type of epitope

type 1 hypersensitivity

anaphylactic or atopic reaction. IgE mediated activation of mast cells and other cell types. B cells are stimulated to produce IgE antibodies against an antigen. IgE will bind to the Fc receptors on the surface of tissue mast cells and blood basophils. these cell will be sensitized and later exposure to the same allergen cross links the bound IgE on sensitized cells resulting in anaphylactic degranulation and the synthesis of leukotrienes and prostaglandins (which cause vasodilation and smooth muscle contraction). histamine release will increase vascular permeability, vasodilation, and bronchioconstriction protective- helminth infcetions- expulses worms from GI tract and eosinophil mediated killing of worms immunopathologic- hay fever, asthma,cutaneous anaphylaxis, food allergies, systemic anaphylaxis

adaptive immune cells

antibodies and lymphoctes (often called humoral response and cell mediated). adaptive= differentiation of self from non self. adaptive immune cells recognize the antigen in the "wild"

dendritic cells

antigen presentation, costimulatory signals, reactive o2 species, interferon, cytokines

TD (t cell dependent response)

antigen that requires both B and T cells to stimulate and ab response. all protein antigens that contain some epitopes recongized by t cells and other epitopes recognized by b cells. immune responses are characterized by isotope switching, affinity maturation, and memory

antigen

anything capable of inducing an immune response and is what an antibody binds to,

immunopathologic inactivation or neutralization reactions: MG

autoimmune Ab binds to Ach receptors blocks interaction of Ach to AchR. binding of Ab causes internalization of receptor and its destruction. No Na+ influx. this reduces the complexity of the synaptic cleft

systemic lupus erythematosus (SLE)

autoimmune, body attacks healthy tissue in many parts of the body. end up with recurring bacterial infections

antibody binding to antigen

binding is not covalent, 3D structure is important (lots of electrostatic forces, hydrophobic bonding, hydrogen bonding, van der waals interactions)- these forces allow the antibody to bind with an antigen in the wild. cross reactivity can occur

immunopathologic inactivation or neutralization reactions: Graves disease

binding of Ab to TSH receptor which stimulates thyroid hormone production. thyroid hormones that normally shut down TSH production have no affect on Ab production, so you end up with excessive thyroid hormone production leading to hyperthyroidism

inactivation or neutralization reactions

binding of Ab to epitope resulting in inactivation, neutralization, or abnormal activation. 1. Ab binding to protein (ie toxin) inhibits the toxin's binding ability to bind a substrate or alters the toxin's conformation resulting in the loss of its activity 2. Ab binding to a virus can block its receptors altering viral structure or opsonizing the virus 3. Autoimmune Abs against hormone or NT receptors can either block or activate the receptor

inflammasome

binding of LPS to TLR4 triggers release of casphage which leads to a signal. another signal will combine and will trigger IL-Beta which is huge in inflammation. unstable cytokines that amplify the innate immune response by increasing the amount of interleukin beta. new target for drugs.

complement receptor 1 (CR1)

binds C4b displacing C2b, or C3b displacing Bb cofactor for I. protects blood cells from being lysed

Cq1 receptor

binds immune complex to phagocytosis

IgE

binds mast cells and basophils, cross links when exposed to allergen mediating immediate hypersensitivity through release of inflammatory mediators such as histamine. contributes to immunity to worms/parasites by activating eosinophils Ag binding with IgE antibody induces degranulation, secretion of histamine, heparin, and other pharmacologic agents allergy, hypersensitivity, parasites

innate immunity

born with, always present, quick acting, non specific. physical barriers, phagocytic cells (macrophage and neutrophil), protective chemicals (pH, surface lipids), enzymes, alternate complement pathway

factors involved in opsonization and phagocytosis

c3b, c3bi (microorganism) CR1, CR3 (neutrophils, macrophages)

chronic granulomatous disease pathophysiology

cant fight off common germs because the presence of CGD makes it difficult for neutrophils to produce reactive oxgen compounds (ie superoxides due to defective phagocyte NADPH oxidase) which is needed to kill specific kinds of bacteria. neutrophils are not activated

C type Lectin Receptors (CLR)

carb binding protein domain and recruties calcium for binding. they function in cell to cell adhension, immune response to pathogens, and apoptosis (fungi, protozoa)

T cells

cell mediated immunity .mature in thymus. CD4 and CD8

f-Met-Leu-Phe Receptors

cell surface protein expressed in phagocytic and blood leukocyte cells where it functions to mediate these cells' responses. stimulates killing of the pathogen or removal of the tissue debris

CCR7

chemokine receptor 7. The protein encoded by this gene is a member of the G protein-coupled receptor family. This receptor was identified as a gene induced by the Epstein-Barr virus (EBV), and is thought to be a mediator of EBV effects on B lymphocytes. This receptor is expressed in various lymphoid tissues and activates B and T lymphocytes. CCR7 has been shown to stimulate dendritic cell maturation. CCR7 is also involved in homing of T cells to various secondary lymphoid organs such as lymph nodes and the spleen as well as trafficking of T cells within the spleen. Activation of Dendritic cells in peripheral tissues induces CCR7 expression on the cell's surface, which recognize CCL19 and CCL21 produced in the Lymph node and increases dendritic cell expression of co-stimulation molecules (B7) and MHC class I or MHC class II.

CXCL8

chemotactic factor that recruits neutrophils, basophils, and T cells to site of infection

c2 disease defects

classical pathway activation defect. can lead to lupus, vasculitis, glomerulonephritis, pyogenic infections usually more bacterial infections

c3 disease defect

classical pathway and alternative pathway activation defect 'pyogenic infections, glomerulonephritis, immune complex disease can lead to death if not put on antibiotics

C domains

code regions important for mediating secondary biological functions

V domains

code the paratope and binds antigen. unique to each antibody

carrier proteins

conjugate with happiness to generate a response

alternative pathway

constant low level AP activation by hydrolysis of thirster bond on C3 "tickover." primary activation via complex macromolecules on surface of pathogens (LPS, bacteria, viruses, fungi). main role is to amplify complement activation. very potent and turns itself over very rapidly.

NADPH oxidase

converts oxygen to superoxidase ion. superoxidas dismutase converts the superoxide to hydrogen peroxide and peroxidase enzymes and fe further convert the hydrogen peroxide to hypochlorite ions and hydroxyl radicals

conjugate vaccine

created by covalently attaching a poor antigen to a strong antigen thereby eliciting a stronger immunological response to the poor antigen. Most commonly, the poor antigen is a polysaccharide that is attached to strong protein antigen. B cell response to a capsular polysaccharide is T cell independent, meaning that B cells can produce antibodies without T cell stimulation.By conjugating the polysaccharide to a protein carrier, a T cell response can be induced

Inflammatory response

cytokines produced by macrophages cause dilation of local small blood vessels, leukocyes move to the periphery of the blood vessel due to increased expression of adhesion molecules, leukocytes extravasate at site of infection and blood clotting occurs in the microvessels

Ig Hinge regions

def 1- short span of aa between 1st and 2nd C domains; rich in cys and pro which provides for flexibility of the molecule. def 2- flexible AA stretch within the heavy chains, rich in cya and pro, has a variable aa sequence.

systemic lupus erthematosus

defect in classical pathway activation in c1q, c1r, c1s c4, c2

defect in c5678

defective MAC that can lead to disseminated naisserial infections

properdinm, factor d defect

defective alternative pathway, can lead to neisserial infections and other pyogenic infections

t cell activation

dendritic cells are great at this. requires both antigen and co-stimulation

antigen presenting cells

dendritic cells, macrophages. capture antigens for display to lymphocytes; display antigens complexed with MHCs on their surfaces

immune complex reactions: type 3 hypersensitivity

deposition of AgAb complexes leading to attraction of polymorphonuclear leukocytes (PMN, PML), inflammation. soluble or insoluble (large) complexes form b/w IgG and IgM and are deposited in tissue. the complexes fix complement (releasing C3a, C5a) resulting in mast cell degranulation and attraction of neutrophils. inflammatory response can aid in clearing bacteria; complement activation, release of neutrophil lysosomal contents can cause tissue damage 1.A 2. C 3. I- immune complex reactions; IgG or IgM bind to antigen, complexes deposit in various tissues, complement activated in target tissues. (lump-I-bump-I) 4. D

factor H defect

deregulated alternative pathway activation, consumption of c3 pyogenic infections and glomerulonephritis and macular degeneration

decay accelerating factor (DAF) and CD59 defect

deregulated c3 converts activity and increased susceptibility of erythrocytes to MAC mediated lysis complement activated intravascular hemolysis and paroxysmal nocturnal hemoglobinuria DAC interferes with the formation of c3 convertase and therefore, the formation of MAC; CD59- prevents C9 from polymerizing and therefore the MAC complex cant be formed. a reduction in the expression of these proteins on RBCs can lead to paraxysomal nocturnal hematoglobinuria (lysis of RBCs)

defect in c1 inhibitor

deregulated classical pathway activation, consumption of c3 associtated with acute intermittent attacks of skin and mucosal edema or hereditary angioneurotic edema

IgD

don't found in significant amounts in the serum. involves initial Ag triggering of B cells while bound to the membrane on the surface of B cells. membrane bound, on cells that haven't yet been activated

t independent antigens

don't require T cells for antibody production. antigen is typically polymerized (polysaccharide) with repeating epitopes, only produce IgM isotopes. so if T cells cant be engagedd then you get the absence of signal to change Ab isotope and so immunological memory cannot be generated

age related macular degeneration (AMD)

due to an overactive complement system

LAD pathophysiology

due to lack of expression in the leukocyte membrane Beta-2 integrins whose main function is to allow neutrophils to make their way out of the bloodstream to the infected tissues by adhering to different ligands expressed in the endothelium.(ie ICAM) these pt's neutrophils cant move towards the site of tissue damage and the neutrophils cant fight against bacteria in these tissues. the bacteria can then proliferate leading to symptomatic infections which can spread and cause damage to other tissues. could be due to chemokinase or ICAM damage

T cell receptor

either an alpha beta antigen binding site or a gamma delta. alpha and beta is the major.

HLA

encodes MHC proteins in humans, has many dif alleles allowing them to fine tune the adaptive immune system

T cells

enter lymph node cortex from the blood via high endothelial venues. T cell activated by antigen on dendritic cells start to proliferate and loose the ability to exit the lymph node. activated T cells differentiate to effector T cells that can exit the lymph node so they can go to where they need to go to fix damage

MHC1

every cell in body with a nucleus expresses this, except RBC

type 3 hypersensitivity

excess of antigen leading to formation of immune complexes being formed that fix complement and are not cleared into circulation. the uncleared immune complexes that cant be cleared by macrophages insert themselves into small blood vessels, joints, and glomeruli. such deposits in tissues induce an inflammatory response and can case damage wherever they precipitate. the cause of damage is the result of c3a and c5a complement anaphylotoxins which mediate granule release from mast cells and recruit inflammatory cells into the tissue so vasculitis, glomelonephritis, and arthritis are commonly associated conditions; as is serum sickness, SLE, rheumatic fever lumpy bumpy basement membrane deposits

NKT cell

for lipids and glycolipids. CD1 is a surface glycoprotein which can present lips/ glycolipids to T cells. non MHC encoded/non polymorphic. expressed in association with B2 macro globulin (on MHC1) ; it binds to hydrophobic regions of a lipid exposing polar region to a NKT cell for T cell interaction. it is seminvariant and can bind only with CD1d

The T cell receptor CD3 complex

for t cell to work, it must be bound to a CD3

MHC 1 receptor

has 3 EC domains (a1, a2, a3) non covalent association with a beta 2 micro globulin

paroxysmal nocturnal hemoglobinuria (PNH)

have destruction of the RBCs, get blood clots, and impaired bone marrow function bc you are not making enough RBCs components. due to a biochemical defect in which the person cannot synthesize GPI anchor that binds proteins to cell membrane.

macular degeneration

have mutations in factor H ending up with high levels of complement activation occurring

CD4+ T cells

helper T cells that help B cells make antibodies and produce cytokines to recruit phagocytes and activate other leukocytes

B cells

humoral immunity; recognize antigen and go through hypermutation to optimize antigen specificity, they produce ANTIBODIES- which differentiate into plasma cells to secrete specific immunoglobulins. maintain immunologic memory to accelerate future response

hypotholamus

increased body them--> decreased viral and bacterial rep; increased antigen processing; increased specific immune response

herd immunity

indirect protection from infectious disease that occurs when a large percentage of a population has become immune to an infection, thereby providing a measure of protection for individuals who are not immune. In a population in which a large number of individuals are immune, chains of infection are likely to be disrupted, which stops or slows the spread of disease. The greater the proportion of individuals in a community who are immune, the smaller the probability that those who are not immune will come into contact with an infectious individual

chemokinase

induce directed chemotaxis in nearby responsive cells and act as chemoattractant to guide the migration of cells. their release is stimulated by proinflammatory cytokines and act as chemoattractants for leukocytes recruting monocytes, neutrophils , and other effector cells from the blood to the site of infection or tissue damage. (innate and adaptive immunity)

innate immunity 0-4 hrs

infection --> recognition by preformed, nonspecific and broadly specific effectors--> removal of infectious agent

adaptive immunity (late >96hrs)

infection --> transport of antigen to lymphoid organs--> recognition by naive B and T cells --> clonal expansion and differentiation to effector cells--> removal of infectious agent

innate immunity 4-96hrs

infection--> recognition of microbial associated molecular patterns--> inflammation recruitment and activation of effector cells--> removal of agent

lysozomes

inflammatory mediator that destroys bacterial cell wall

complement

inflammatory mediator that lyses pathogen or infected cell

leukotrienes and prostaglandins

inflammatory mediator that vasodilates increases vascular permeability

cytokines and interferons

inflammatory mediators that activate other immune components

t reg cells

inhibit dendritic cells, prevents autoimmunity, and supresses T cell

TAP 1 and 2

internally derived proteins/peptides are degraded by proteasome and these degraded proteins are carried into the RER by the transporter of antigen peptides (TAP). upon protein binding the interaction of class 1 MHC chain and beta 2 micro globulin is stabilized and the complex is routed through golgi into the PM . mutation in TAP cant get the peptide loaded into MHC

NOD- like receptors (NLRs)

intracellular sensors that enter cell via phagocytosis or pores. pattern recognition receptor that cooperates with TLRs to reg. inflammatory and apoptotic response. found in lymphocytes, macrophages, dendritic cells, and non immune cells.

C3

is cleaved by c3 convertase. the fragments of c3 participate in osponization and clearance of bacteria as well as the generation of c5 convertase leading to the formation of the membrane attack complex. phagocytosis/clearance (C3b/iC3b)

Toll like Receptors (TLRs)

key role in innate immune response. membrane spannning receoptors expressed on macrophages and dendritic cells and recognize structurally conserved sequences from microbes. when microbes breach physical barrier they are recognized by TLR which activates immune cell responses. have dif typed of TLRs and some are external and internal

CD8+ T cells

kill virus infected cells

superoxide production by neutrophils

killing and digestion of neutrophils depend on o2 consumption by the NADPH oxidase which generates superoxides (o2-)

IL-6

lymphocyte activation and increased antibody production; systemically causes fever and induces acute phase protein production by hepatocytes

natural killer cells

lysis of viral infected cells, interferon, macrophage activation

IgG

main antibody in serum, fixes complement activation, crosses the placenta, opsinizes bacteria, neutralizes bacterial toxins and viruses. long life and has 4 subclasses which differ in the number and arrangement of the interchain and disulfide bonds resulting in dif functional properties. smallest mw, high affinity, in serum, antiviral/bacterial

multivalent multideterminant

many epitopes, different specificities (proteins). Ab linkage is larger and more complex

multivalent unideterminant

may epitomes with same specificity (polysaccharides); Ab cross linking can occur

C5b- C9

membrane attack complex

membrane cofactor protein (MCP)

membrane protein that promotes C3b and C4b inactivation by I

innate immunity

microbiological flora also plays a role

complement system

more than serum and cell surface proteins involved in inflammation and immunity. primary humoral defense against bacterial and viral infections. activation is initiated by the presence of antigen antibody complexis, foreign surfaces, or pathogenic organisms

neutrophils

most common leukocyte in the plasma that is the first line of defense against microorganisms. very mobile and will respond to a variety of chemical signals. they enhance their phagocytosis in conjunction with specific antibodies

somatic hypermutation

mutations that occur in the V genes of heavy or light chains over the life of the B cell, usually after activation

t cell costimulation

needed for activation of T cells in response to MHC restricted antigens upon T cell binding to MHC . example= B7 and CD 28

CD4+

needed for antibody class switching

hyporeactivity (immunodeficiency)

neutrophil disorders, antibody deficiency, complement deficiency, T cell dysfunction

bone marrow endothelium

neutrophil mobilization--> phagocytosis

T independent antigen (TI antigen)

non protein antigens such as polysaccharides and lipids that stimulate Ab responses without the help of helper T lymphocytes. contain multiple identical epitopes that can cross link antigen receptors of mature B cells thereby activating the cells. kids under 2 don't have a lot of mature B cells, so they cannot produce antibodies toward polysaccharide antigens

MHC 2

on APC exogenous ag processing. the invariant chain prevents peptide binding to class 2 molecules within the ER and facilitates routing to endosoems. late stage of endosome containing class 2 MHC molecules and the invariant chain fuse with lysosome, enzymes within the lysosomes degrade the invariant chain enabling class 2 MHC to bind peptides

epitope

part of the antigen that the paratope recognizes and binds to "the key". an antigen may have several of these

complementarily determining region

part of the variable regions in Ig and T cell receptors, generated by B cells and T cells, where these molecules bind to their specific antigen. a set of these constitutes a paratope and are crucial in the diversity of antigen specificity generated by lymphocytes. if an IgG- has two binding sites, so a total of 12 of these

neutrophils, eosinophins, basophils, and mast cells

phagocytosis and intracellular destruction of microorganisms

macrophage

phagocytosis, inflammatory mediator, reactive O2 and N2 species, antimicrobial peptides , cytokines, complement proteins

neutrophil

phagocytosis; reactive O2 and N2 species, antimicrobial peptides

adjuvant

pharmacological or immunological agent that modifies the effects of other agents. may be added to a vaccine to modify the immune response by boosting it such as to give higher amounts of antibodies that last longer this minimizing the amount of injected foreign material

conjugate vaccines

polysaccharide alone generates IgM in a thymus independent fashion but a polysaccharide conjugated to a carrier protein generates a thymus dependent antibody response (isotope switching)

Fc portion

portion of antibody that allows for the interaction of immune complexes with theory cells. many dif forms exist that may be regulatory or stimulatory

monocytes, macrophages, dendritic cells

present foreign antigens to lymphocytes

C3a and C5a

pro-inflammatory mediators; anaphylatoxins are generated as products of complement activation

osponization

process by which a pathogen is marked for ingestion and eliminated by a phagocyte.

IgM

produced in the immediate response to an antigen. (most efficient) it fixes complement but does not cross the placenta. antigen receptor on the surface of B cells. pentamer allows avid binding to antigen while humoral response evolves. the J chain stabilizes pentamer. doesnt undergo a lot of hypermutations (it's affinity is not high) but is really good at binding tightly (high avidity), so its avidity increases its functional affinity; potent agglutinator-(up to 10 paratopes/molecules) highest mw, highest avidity, 1st to appear in response, good at activating complement, antibacterial

Cytotoxic reactions: protective and immunopathogenic

protective- Ab and complement mediated killing and osponization of pyogenic bacteria (Staph or strep); ab and complement mediated killing and opsonization or protozoa including plasmodium (malaria) and trypanosoma (sleeping sickness) immunopathologic- transfusion rxns, lysis of transfused RBCs; Rh reactions- hemolytic disease in newborns; hemolytic anemia- ab lyse and opsonize RBCs; GoodPasture's syndrome- antibasement membrane Abs; Transplant rejection- recipient Ab cause hyper acute rejection

fat, muscle

protein and energy mobilization to allow increased body temp --> decreased viral and bacterial rep; increased antigen processing; increased specific immune response

macrophages

quaterbacks of inflammation and secrete proinflammatory cytokines (IL-1B, TBF- alpha, IL-6, CXCL8, IL-12)

hapten

reacts with an antibody but is not immunologic by itself and must be conjugate to a suitable carrier. essentially an incomplete antigen i.e. penicilin

natural killer cells

recognize altered features on the membranes of abnormal cells; controlled by killer inhibitory receptors, can also mediate cell killing through ADCC

pattern recognition receptors

recognize evolutionarily conserved structures shared by classes of microbes (TLRs ,NLRs, CLR,fMLP)

th17

recruits neutrophils and secrete IL 17

factor I defect

regulated classical pathway activation and consumption of c3 pyogenic infections and immune complex disease

Factor H

regulates alternative pathways. it binds c3b displacing Bb for I

complement system pathways

1. classical (mainly IgG and IgM immune complexes) (IgM> IgG3> IgG1>IgG2) (IgG4, IgA, IgD, IgE don't activate) 2. alternative 3. MBP (lectin) pathway- activates the classical pathway in the absence of antibody ** central component is C3 which is cleaved by c3 convertase. the fragments of c3 participate in osponization and clearance of bacteria as well as the generation

complement system functions

1. cytolysis of foreign organisms (bateria) 2. opsonization and phagocytosis of foreign organisms 3. activation and directed migration of leukocytes 4. solubilization and clearance of immune complexes 5. enhancing humoral immune response

sensitization and response phase of IgE

1. first exposure to pollen leads to IL-4 driving B cells to produce IgE in response to pollen antigens; pollen specific IgE bind to mast cells; second exposure to pollen leads to the acute release of mast cell contents causing allergic rhinitis

T cell cytotoxicity

1. perforins- pore formation 2. granzymes- proteases that degrade cell components activation of apopotosis is triggered by Fas-fas ligand binding which activated JUN kinase, capsase B; this process is aided by granzymes and causes destruction go mitochondria protective- viral infections, cancer immune surveillance, recognition of TSTAs, intracellular pathogens. immunopathologuc- autoimmune diseases, contact dermatitis, viral exanthems, allograft rejection

protective inactivation or neutralization reactions

1.toxin inactivation (ie C. diphtheriae and C tetani toxins) 2. virus neutralization (polio, influenza, MMR)

light chains

2 types: kappa chains (60%) and lambda chains (40%); 3 HV regions

complement system

30 plasma and cell surface proteins that function in inflammation and is susceptible of changing when subjected to heat

heavy chains

5 classes in humans. similarities in aa sequence but each class has unique sequence; named with greek letters corresponding with class name IgG, IgA, IgM, IgE, IgD; have 3 hyperbariable regions

Type 2 hypersensitivity reaction

Ab binds to cell surfaces resulting in osponization (by IgG or C3b enhance phagocytosis), complement activation/MAC (pore forms that lyses the cell) formation or the Ab dependent cellular cytoxicity (ADCC) 1. A 2. C- Cytotoxic. IgG or IgM bind to cell receptor, Complement activation +/- NK cell activation, death of "self" cells Cmooth (smooth) 3. I 4. D

type 2 hypersensitivity

Ab produced by the immune response bind to antigens on the pts own cell surfaces which are recognized by macrophages or dendritic cells. this causes a B cell response and antigens are produced against the foreign antigen. ie- ABO blood incompatibility where RBCs have dif antigens causing them to be recognized as dif. IgM and IgG antibodies will bind to these antigens to form complexes that activate the classical pathway to eliminate the cells. MAC complexes cause lysis and cell dead. other examples include hemolytic anemia, and ach receptors MG; Good pasture's syndome where the basement membrane in the lung and kidney are attacked by one's own AB; ADCC

factors involved in activation of inflammation (c3a, c4a, c5a)- anaphylatoxins

smooth muscle contraction, histamine release from mast cells, increase in vascular perm C3a and C5a are known for attracting WBCs to infections. potent chemoattractants (same with C4a) C3a more for allergies c5a (CD88)- neutrophils, monocytes, macrophages, eosinophils c3a- easonophils

CR4

specificity- C3bi function- stimulates phagocytosis cell types- macrophages, monocytes, polymorphonulcear leukocytes, FDC

CR2 (CD21)

specificity- C3d C3dg C3bi Epstein Barr Virus (EBV) function- part of b cell coreceptor, EBV receptor cell types- B cells and FDC expressed in B cells and dendritic cells; enhances the immune response

CR1

specificity- c3b, c4b function- promotes c3b and c4b decay, stimulates phagocytosis, erythrocyte transport of immune complexes cell types- erythrocytes, macrophages, monocytes, B cells, FDC involved in clearing immune complexes *C3b, C3bi= microorganisms and are expressed on bacteria

I-CAM-1

stabilizes cell cell interactions and faciliteates leukocyte transmagration (from blood to tissue). its ligation produces proinflammatory effects such as inflammatory leukocyte recruitment

immunogen

stimulus that produces a humoral or cell mediated immune response.

superantigens

superantigens bind to T cell receptors and MHC without processing. they are presented by MHC but not in peptide groove. this process involves the direct interaction of the V beta region of TCR which activate any T cell expressing specific V beta TCR segment. this leads to a non specific activation of a large number of T cells cause a nonspecific activation of T cells resulting in polyclonal T cell activation and massive cytokine release. the antigen is not processed and presented to T cells. intact molecule binds to MHC2 and crosslinks it with the beta chain of the CD4+ T cells

leukocyte adhesion deficiency (LAD) symptoms

symptoms recurrent bacterial infections, leukocytosis, gingivities.

hyperreactivity (immunopathology)

systemic autoimmunity, organ specific autoimmunity, allergies and asthma, pathogen induced pathology, SLE

Fragmented Crystallin region

tail region of antibody that interacts with cell surface receptors and some proteins of the complement system. allows antibodies to activate the immune system. constant, carboxy terminal, complement binding, carbohydrate side chains. it determines isotope (IgM, IgD, etc). many forms of FcR exist and may be regulatory or stimulatory

C1

C1 complex is comprised of C1q, C1r, and C1s. C1q has six "heads" which can bind an IgG. At least two of these heads must be occupied to induce the required conformation for deposition of the components C1r and C1s, a requirement which can be met only in immune complexes and not by circulating monomeric IgG. IgG1 or IgG3 binding to C1q activates C1s to become a protease which cleaves complement component C4 into C4a and C4b.

Membrane attack complex

C5 is cleaved into C5a and C5b where C5b can bind C6 and C7. The c5bc6c7 has hydrophobic regions that permit insertion into the membrane. subsequent binding of C8 allows some leakage from the inside out but it is accelerated by the inclusion of C9. C9 pokes holes in the membrane and kills bacteria

costimulatory factors

CD 40 = important ligand for ab class switching CD28= binds to B7 to start producing IL-2

Human Ig Domains

CH2 (constant heavy chain region 2)- binds C1q and controls catabolic rate CH3- interacts with the Fc receptor of macrophages and monocytes; non covalent assembly of heavy chains CH1+CH3= assembly with protein A from strep and interacts with Fc receptor VH+ VL= antigen binding

terminal deoxyribonucleic transferase (tdt)

DNA pol in immature B and T cells. adds N nucleotides to the VDJ exons of the TCR and BCR during recombination allowing for junctional diversity. junctional diversity results in change in antigen binding sites

ajdvucts and effects on immune response

these enhance the immune response by increasing the 1/2 life of immunogen, increasing local inflammation, and improving processing and presentation by MHC. only aluminum phosphate and aluminum hydroxide are approved for use in human vaccines

Ig Idiotypes

they provide a natural autoimmune mechanism for regulating Ab levels and anti id antibodies are routinely found and down regulate production of Ab. natural autoimmune mechanism for regulating Ab levels shared characteristics between a group of immunoglobulin molecules based on the antigen binding specificity and therefore structure of their variable region. The variable region of antigen receptors of T cells (TCRs) and B cells (immunoglobulins) contain complementarity determining regions (CDRs) with unique amino acid sequences. They define the surface and properties of the variable region, determining the antigen specificity and therefore the idiotope of the molecule.