Component of gram negative bacterial cell walls recognized by the innate immune system. Also known as endotoxin.

Leads to danger signalling through a toll-like receptor. Is phagocytosis and example of innate or adaptive immunity? Name 3 cell types that are mainly involved with innate immunity.

LPS (lipopolysaccharide)

Innate Macrophages, NK cells, neutrophils

Type of immunity that is present at birth, involves recognition of patterns, has a Innate immunity relatively rapid response, and rejects via primitive effector mechanisms. Type of immunity that develops only in response to challenge, invovlves lymphocytes recognizing the epitopes of antigens, has a more delayed response, Adaptive immunity creates memory cells, and rejects via primitive and sophisticated effector mechanisms Lymphocytes that are capable of becoming plasma cells and producing antibodies. When are B cells committed to the antigens they recognize? Which cells have membrane-bound antibodies as their receptors for an antigen? Which MHC molecules do Cytotoxic (CD8+) T cells recognize? Which MHC molecules do Helper (CD4+) T cells recognize? Patterns recognized by the innate immune system. B cells When they are produced (they are born that way) B cells MHC I MHC II Pathogen associated molecular patterns (PAMPs)

As part of the innate immune system, Defensins Paneth cells (epithelium of the small intestine.)

in the gut mucosa secrete these antimicrobial enzymes in response to microbes via the recognition of patterns. Group of proteins that lyze membranes. Some of them are chemotaxins and/or Complement opsonins. Name the three complement pathways. Are toll-like receptors part of the innate or adaptive immune system? Is phagocytosis a component of innate or adaptive immunity? Alternative, Classical, Lecithin pathways Innate Innate

A protein that binds to microbial structures and enhances their binding to Opsonins phagocytic receptors on cells. C3b, antibodies (especially IgG), and Mannose-binding protein are examples of this type of protein that facilitate phagocytosis. Opsonins

Enzyme needed to begin the respiratory burst within phagocytes such as neutrophils and macrophages. Creates NADPH oxidase superoxide from molecular oxygen. Deficient in Chronic Granulomatous Disease. Enzyme that creates hydrogen peroxide Superoxide dismutase and oxygen from superoxide anion. What is "danger signalling." What do these have in common: lipoteichoic acid, formyl-methionyl peptides, C5a, LTB4, IL-8 Immune cells are stimulated to secrete cytokines to communicate with other immune cells. They are chemotaxins (memorize)

Reduces antigen burden, activates How does innate immunity prepare the APCs, induces cytokines that host for an adaptive immune response? promote antibody production,

activates complement to produce Bcell activating peptides Is acute inflammation mostly due to innate or adaptive immunity? Two important genuses of gram + bacteria. Innate Staph and Strep

What do these have in common: Mycobacterium, Legionella, Salmonella, Intracellular bacteria Listeria Organism that may form a "fungus ball" in the lungs or sinuses, especially in immuncompromised individuals. Cardinal signs of inflammation. Aspergillus Redness, Heat, Pain, Swelling, (loss of function)

Redness (caused by vasodilation), Histamine creates the triple response flare (redness surrounding intial when injected intradermally. What are area, caused by axonal reflex), and the three components of this response? wheal (swelling due to increased capillary permeability) Cytokines produced by macrophages to IL-1, TNF-alpha initiate and inflammatory response. Cytokine produced by NK cells in innate responses and T cells in adaptive INF-gamma responses to activate macrophages. What do these have in common: TGFbeta, IL-10, lipoxins, cholinergic discharge Give the order of cell type arrival to an area of inflammation. Anti-inflammatory Neutrophils (within 24 hours), Macrophages (48 hours), Fibroblasts (72 hours)

Excessive contraction of a wound. May occur in Peyronie's disease, burns, or in Contracture the hands (Dupuytren's) Where are naive T cells (T cells that have never encountered an antigen) found? Lymph nodes and spleen

Where are effector T cells found? Lymph node location of B cells. Lymph node location of T cells and dendritic cells. Lymph node location of plasma cells. Name for dendritic cells found in skin.

Sites of inflammation Cortex Paracortex Medulla Langerhans cells

Cells that recognize pathogens via their PAMPs, phagocytose the pathogen, Dendritic cells migrate to lymph nodes and present the antigen to naive T cells there MHC class that contains alpha chain and beta2 microglobulin components. Name the three major MHC class I loci in humans (they each encode an alpha chain). Which cells express MHC class I molecules? MHC class I HLA-A, HLA-B, HLA-C Virtually all nucleated cells (except trophoblasts)

MHC class that contains alpha and beta MHC class II chains (both encoded by MHC genes). Name the three major MHC class II loci in humans (they each encode both an alpha and beta chain). How many different MHC alleles do each cell express? HLA-DP, HLA-DQ, HLA-DR Multiple MHC molecule binds invariant chain, Invariant chain cleaved in endosome to leave CLIP, fusion with antigen-containing endosome makes CLIP fall off so peptide antigen can bind MHC, presentation on cell surface Bare lymphocyte syndrome II

Describe the events leading to Class II antigen presentation by phagocytes.

Defect in MHC stimulating transcription factor CIITA leads to this syndrome where expression of MHC class II molecules is absent.

Describe the events leading to Class I antigen presentation by cells. Cells that recognize glycolipid antigens bound to CD1 molecules (which are similar to class I MHC molecules) HLA antigen whose expression is associated with the seronegative spondyloarthropathies (e.g., ankylosing spondylitis, Reiter's syndrome, IBD) HLA antigen associated with Celiac disease. A mutation in the HFE (HLA-H) gene is associated with this disease of overactive intestinal iron uptake and total body iron overload.

Intracellular pathogen (e.g., virus) is degraded by proteasome, TAP transport antigens into ER, MHC I molecules bind to antigen here and are transported to the cell surface NKT cells

HLA-B27

HLA-DR3

Hereditary hemochromatosis

Name some DAMPs, which like PAMPs are recognized by TLRs. They are part DNA, ATP, adenosine, uric acid, of inflammation moreso than innate heparin sulfate, hyaluronan immunity in general. Portion of an antigen that binds to a T cell receptor or antibody. Microbial antigen that cross-links and MHC molecule and TCR by binding outside of the peptide-binding groove, leading to a dramatic polyclonal T cell response and cytokine storm. The most famous example of a superantigen. Epitope

Superantigen

Toxic shock syndrome toxin (TSST) produced by Staph aureus.

Is the part of the antibody that binds antigen (the complementarity determining region/hypervariable region) Both part of the heavy chain or the light chain?

Antibody fragment that binds antibody.

Fab fragment

Antibody fragment that does not bind antigen but may bind to immune cells or Fc fragment to complement. Name the antibody light chains. Name the antibody heavy chains. Antibody isotypes that form multimers. The strength with which a ligand interacts with a binding site. The strength of a protein-protein interaction when multiple binding sites are possible. Enzymes in lymphocytes involved with recombination of immunoglobulin and TCR genes. Enzyme in lymphocytes responsible for adding or subtracting nucleotides to joining regions between V, D, and J regions of immunoglobulin genes. Apoptosis of immature B or T cells due high affinity to self antigens. Survival of B or T cells because of low affinity binding to self-antigens. Naive B cells that survive the selection process coexpress these two antibody isotypes on their cell surface. Kappa and lambda alpha, gamma, delta, epsilon, mu (which respectively create the Ig isotypes of IgA, IgG, IgD, IgE, and IgM) IgA and IgM Affinity Avidity

RAG-1 and RAG-2

TdT

Negative selection Positive selection IgM and IgD

Put these in order of their production in the thymus: double positive thymocytes, Double negative, Double positive, double negative thymocytes, single Single positive positive thymocytes Thymocyte population that undergoes positive selection in the thymus. Double positive thymocytes

Dilation/partial destruction of bronchial walls due to chronic infections with inflammation.

Bronchiectasis

Question NK cells Main Functions of Antibody

Answer * Activated by altered self (change in cell surface components) or missing self (absence of normal cell surface components) * Activated by IL-12 and TNF * Secretes IFN-gamma (1) Neutralize toxins/virus (2) Opsonize bacteria (3) Complement activation

Antibody IgG > IgA > IgM > IgD > IgE Concentrations (serum) * Major isotype of circulating serum Ab; longest halflife * Only isotype to cross placenta * Fixes complement; acts as opsonin; stimulates chemotaxis * Only immunoglobulin to cross the placenta * 4 subclasses * Main Ab in secondary response * Pentameric (10 binding sites) secreted IgM - held together by J chain * first Ig produced after Ag exposure * First secreted Ab produced during primary response * Most potent activator of the complement system * Found on naive B cell - acts as BCR Present almost exclusively in membrane form on B cells Functions as antigen receptor in activation of B cells Predominant antibody isotype in external secretions (e.g., saliva, mucus, breast milk) Mostly as monomer in serum and as dimer in secretions Acquires secretory component as it moves across epithelial cells Prevents adherence of microbes to mucous membr Mediator of type I (immediate) hypersensitivity and promotes antiparasitic responses Binds tightly to Fc receptor on mast cells, basophils and sometimes eosiniphils VDJ recombinase - contains RAG 1 and RAG 2 * LFA-1 (integrin) on T cell and ICAM-1 on APCs * T

IgG

IgM

IgD

IgA

IgE Mediators for V(D)J recombination Adhesion molecules

during T cell activation

cell's affinity can be increased by chemokines at the site of infection * B7 proteins on APCs which recognise a receptor called CD28 * CD40 ligand on T cells and CD40 on APCs - activates APCs to increase B7 expression and to secrete cytokines like IL-12 (inc differentiation of T cells) CTLA-4 (inhibitory receptor) can recognise B7. Knocking them out in mice causes excessive lymphocyte expansion and autoimmune disease. IL-2 - increased conc. and increased expression of IL-2 receptor Also called T cell growth factor, stimulates survival and proliferation of T cells CD40L - transcribed in T cells in response to Ag recognition and costimulaiton Binds to CD40 (APCs) - activates the cells Stimulates expression of costimulators and cytokines Transcription factor: T-bet Secretes: * IL-2 * IFNgamma: Macrophage and NK cell activator. HLA Ag presentation by endothelial cells. Downregulates IL-4 secretion by Th2. * TNF-gamma: activates macrophages Transcription factor: GATA-3 SECRETES: * IL-4 switch to IgE prod'n (mast cell degranulation) * IL-5 stimulates growth of eosiniphils PROMOTES HELMINTH AND WORM responses * IL-10 and IL-4 -- downregulates IFN-gamma by Th1 (suppress CMI) Transcription factor: RORgammat SECRETES: IL-17 and IL-22: promotes inflammation and autoimmunity Recruits neutrophils and maintains barrier function Express FoxP3 Express high affinity IL-2 receptor (CD25) Binding -> ^ in IL-10 which has antiinflammatory properties) Tregs outcompete naive CD4 T cells for IL-2 Suppression mediated by CTLA4, TGFB, IL-10, IL-35 Activated macrophages -> ^ TNF and IL-1 -> ^ Eand P- selectins and VCAM-1 and ICAM-1 Activated

Costimulation and B cell activation Limiting immune response (opposing costimulation) First secreted cytokine due to T cell activation Most important cell surface protein involved in the effector function of CD4+ T cells

Th1

Th2

Th17

Tregs

Migration of effector T cells

T cells ^ LFA-1 and VLA-1, ligands for selectins and lose L-selectin (attracts T cell to lymph node) Express receptors for chemokines prod by macrophage T-independent T-dependent Restricted to IgM response Without Th help No isotype switching, affinity maturation or prod'n of memory cells Proteins Isotype switching, affinity maturation, secondary response

Primary vs secondary B Primary - slow onset, initially Igm, low titre cell response Secondary - fast onset, primarily IgG, high titre Follicular B cells Marginal zone B cells Located in follicles Bulk of T dependent, class switched, high affinity Ab responses and memory IgG IgA IgE GC reaction Margins of splenic white pulp Responds to blood borne polysaccharide Ag Mainly IgM B cells express CXRC5 and are attracted to follicles by ligand CXCL13 Naive T cells express CCR7 which are attracted to CCL19 and CCL21 in T cell zone A B cell helping T cell will upregulate CXCR5 Activate ed B cells will upregulate CCR7 (T cell Complement products such as C3d binds to CR2 and this increases Ag-dependent activation of B cells

How do B cells and T cells get together? 'Second signal' for B cell activation

T-DEPENDENT AB RESPONSES AND AB CLASS SWITCHING No CD40L - predominately IgM, Significance of CD40L recurring bacterial infections, no GC centers, no in T cell help for B cells somatic hypermutation, no Ig isotype switching, no memory cells Class Switch Effector function of B cells Mucosal immunity CD40L and cytokine signals from T cells may activate switch genes. AID (activated by CD40L) plays key tole in making nucleotides susceptible to recombination. Neutralisation Opsonisation and phagocytosis Many microbes inhaled or ingested, DCs sample, Ag and activate T cells --> TGFB and induces class

switching to IgA IgA actively transported Protease cleaves IgA, but leaves part of its poly-Ig receptor (protection) Maternal IgG across placenta to the fetus and through the intestines after birth through breast milk Primary lymphoid tissues T cells: negative selection. AIRE expresses peripheral tissue antigens and if it reacts to self will be apoptosed. B cells: interact w/ self -- change their receptor specificity or are killed. If this fails, death signal.

Central tolerance

T cell anergy due to lack of second signal during Peripheral tolerance (T activation OR negative costimulatory molecules cell) Tregs - IL-10, TGFB blocks activation of lymphocytes and macrophages Activation induced cell death Fail to receive T cell help T-independent Ag only Peripheral tolerance (B trigger a B cell response when signals are strong cell) Anergic B cells leave the follicles but excluded from reentering other lymphoid follicles Tumor immunity How are alloantigens detected? Immune system destroys allografts in three main ways: Hyperacute T cells may recognise allogeneic MHC molecules in the graft displayed by DCs in the graft (DIRECT) or by DCs in the host (INDIRECT) * alloreactive CTLs in the indirect pathway cannot recognise and kill cells in the graft. CD4+ T cells - DTH Thrombosis and necrosis of graft Due to circulating Ab specific for antigens on graft endothelial cells Bind to Ag and activate complement and clotting systems - injury to endothelium

T cells which react against alloantigens in the graft Immune system vascular damage. Antibodies may also do this by destroys allografts in classical complement. Solved by three main ways: Acute immunosuppressive therapy? Immune system destroys allografts in three main ways: Chronic Preventing graft rejection Progressive loss of graft function Graft fibrosis, blood vessel narrowing T cells - react against graft alloantigens and secrete cytokines Immunosuppression (glucocorticoids, blocks IL-1 from macs; cyclosporine, interferes with IL-2 prod'n

from helper T cells) Bone marrow transplantation (matching of donor HLA alleles) Induce peripheral tolerance Vaccination: Passive immunisation Vaccination: Prophylactic vaccination Transfer of humoral immunity (giving of Ab) No immune response, no lasting effect IgG through placenta Better for immunocompromised patients Good for people at risk of infection and not enough time to mount response (rabies) Anti-venom Protective immunity against a pathogen using a non pathogenic form. Creates long-lived protective immunity without causing disease. Can't replicate-no disease Attenuated using serial tissue culture passaging-non-human or genetic modification + good memory response, same immune response as wild type + spread to others revert to wild type - immunocompromised people i.e. measles, Inactivation by heat/chemical treatment + no reversion, OK for immunocompromised patients - not as effective - no immune response (no replication) boosters i.e. influenza, hep A Uses parts of original pathogen + increased safety + can differentiate infection from vaccination - limited CTL response - lots of research required - require adjuvants (stimulates immune response) i.e. diptheria, tetanus Carrier protein and attached Ag to enhance immunity Manipulating DCs to target Ags to T cells. Therapeutic, not preventative. Possible uses in tumours - more specific than chemotherapy! Ex-vivo loading of DCs: precursor cells isolated, load onto Ag, mature using cytokines and deliver to patients VERY ha

Active immunisation: live attenuation

Active immunisation: killed vaccines

Active immunisation: subunit vaccines Active immunisation: conjugate vaccines

DC vaccines