ImmunologyFinalReview

Germinal centers

Lectin-type proteins

Naive lymphocytes are inactive and reside in the 2* lymphoid tissue until they meet THEIR SPECIFIC ANTIGEN and differentiate into effector T-lymphocytes which will now act on that antigen

C-3b, Surfactant protein (SP-A), mannose-binding lectin, and C-reactive protein

All NUCLEATED cells

IgA

somatic hypermutation

Total strength of antibody + 2 identical antigens

vesicular compartment

• MHC I = CD8 (cyto)
• MHC II = CD4 (helper)

Recruit non-receptor kinase Lck

pTα

• Heavy/light chain rearrangement during B cell development
• β chain rearrangement during T cell development
• α chain rearrangement during T cell development (delayed)

alloreactive T-cells (react to non-self MHC of same species)

T cell must be weakly attracted to a self antigen presented on an MHC molecule to be positively selected, but will be negatively selected if the affinity is too great

• Constant recirculation through lymph and re-entering 2* lymphoid tissues UNITL antigen is encountered or lymphocyte dies
• antigen encountered: proliferates and differentiates
• dies: new lymphocyte takes its place (# remains constant)

• Regulated trafficking of lymphocytes to sites of antigenic or microbial invasion (via chemokines)
• T: CCR7 recognizes CCL19 and CCL21
• B: CXCR5 recognizes CXCL13

• deletion: strongly cross-linking antigen undergo apoptosis without receptor editing
• anergy: bind an abundant soluble antigen (only weakly cross-linking)
• T cell does not receive appropriate co-stimulation during antigen recognition
• Survival: Inflammation has induced costimulatory molecules on DC
• Thanks to these costimulatory molecules and cytokines the lymphocyte is successfully differentiated in an effector
• Why?: No inflammation = no costim = no PIP3K = no signal transduction

• Naive CD8 recognize pathogen peptides presented by MHC I
• Tcyto: recognize and kill infected cells
• Naive CD4 recognize pathogen peptides presented by MHC II
• TH1, TH2, TH17, TFH: activate their target cells
• TH1 - infected MO, B cell antibody production
• TH2 - B cell antibody production (esp IgE class switching)
• TH17 - Enahnce neutrophil response
• TFH - help isotype switching, antibody production
• Regulatory T-cells: limit extent of immune activation

• 1. T cell mediated toxicity
• 2. Macrophage activation by effector T cells
• 3. help B cells to trigger antibody production (first step in humoral immunity)

• The activation/clonal expansion of a naïve T cell on its initial encounter with antigen
• DC most important in priming
• CD8 priming -> Tcyto
• CD4 priming -> various Thelper

• Lymphocyte recognition is very effective
• Antigen in node "traps" all specific lymphocytes while they differentiate and proliferate, and will then leave the node (more than entered)

• 1. rolling of lymphocytes along endothelial surface (selectins/addressins)
• 2. Activation of integrins on T cells (activated by chemokines)
• 3. Firm adhesion
• 4. Diapedesis (following chemokine gradients)

• Selectins: surface of T cells
• Vascular addressins: surface of endothelia
• Integrins: surface of T cells
• Ig superfamily: surface of manycells

• Professional: DC, M0, B cells | MHC II | Costimulatory molecules
• Non-professional: nucleated cells | MHC I | no costimulatory molecules

• DC: activates T cells
• Drive the initial clonal expansion and differentiation of naïve T cells
• M0 and B cells: present to T cells to be activated themselves
• Interact mainly with already primed effector CD4 cells

• Conventional DC: present antigens to and and activateing naïve T cells in the adaptive immune response
• Plasmacytoid DC: produce interferon in the innate immune response
• Follicular DC: aid in somatic hypermutation of B cells

• Receptor-mediated phagocytosis: MHC II | CD4
• Macropinocytosis: MHC II | CD4
• Viral infection: MHC I | CD8
• Cross presentation after 1 or 2: MHC I | CD8
• Transfer from incoming dendritic cell: MHC I | CD8

• Tnaive: require costimulation and Ag stimulation from DC for maturation
• Tcyto: only require Ag stimulation (no costim) to destroy infected cell
• TH1: requires Costimulation (CD40/CD40L) from macrophage to activate
• TFH: requires costimulation (CD40/CD40L) to activate B cell

• antigen specific signals: derived from specific peptide:MHC complex with TCR
• co-stimulatory signals: promote survival and expansion of T cells
• signals for T-cell differentiation: promote different subsets of effector T cells (Varies w/ cytokines)
• *IL-2 plays key role in proliferation

• Anergy: T cells are stimulated with antigen in absence of costimulation
• Prevents self-reactive T cell from undergoing clonal expansion
• GRAIL (gene related to anergy in lymphocytes) ubiquitinates CD3, causing degredation and then inability to be activated
• This is prevented by CD28 signalling

• Because the actions are so destructive, additional co-stimulatory activity is needed (two ways)
• 1. In some viral infections DC can directly CD8 after intrinsically increasing co-stim activity
• 2. Most viral infections TH17 CD4 cells that recognize the same antigen provide additional signaling when bound to the same APC (probably DC)
• increasing co-stim activity of DC AND producing IL-2 for CD8 proliferation

• T naïve ----DC---->Effector T (priming)
• TH1: activate macrophages
• TH17: Require for activation of Tcyto cells
• TFH: provide B cell help in follicle
• Treg: regulation

• Apoptosis: cell begins to condense and stops all activity, shrinks but retains cell membrane integrity, trapping pathogens
• Necrosis: cell stops all activity, but is easily lysed and pathogens escape, able to re-infect

• Perforin: forms pores in membrane for delivery of cytotoxic granules
• Granzymes: family of serine proteases that trigger apoptosis
• Granulysin: antimicrobial activity, induces apoptosis in high [ ]
• Serglycin: acts as sscaffold in sorting/packing of perforin and granzymes

• Tcyto reorient their secretory apparatus toward each cell and kill them one by one
• Specific recognition by TCR identifies which target cell to kill
• Polarized release of cytotoxic granules ensures neighboring cells are spared

• hours vs tcyto 5 mins
• TH1 cells must express CD40L and INF-y in order to activate MO.
• It takes time to produce protein expression, therefore the interaction will take longer to progress

• Activation of B cells which produce Ab
• 1. Neutralization
• 2. Opsonization
• 3. Complement activation

• Cross-linking BCRs signal to cell that antigen is bound
• Delivers bound antigen to intracellular sites to be degrades/presented on MHC II (recognized by Tfh which cause proliferation and differentiation)

The B cell doesn't undergo somatic hypermutation therefor they only produce IgM (lower affinity and lower versatility)

• Thymus-dependent: protein antigens (tend to have varied surface structures)
• Thymus-independent: LPS, DNA (tend to have uniform surface structure, very large)
• 2nd signal tends to come from TLR rather than Tcell OR extensive amounts of crosslinkings

The epitopes that activate B cells and T cells should be FROM the same pathogen, but may not be identical epitopes

• TI-1: cause proliferation of B cells regardless of antigen specificity (polyclonal)
• Antigen-specific antibody responses tend to be low
• TI-2: activate only mature B cells (monoclonal)
• long, repeating units

• Prevents secretory IgA from binding to the IgA
• Binds to mucins, acting as glue to bind secreted IgA to mucous layer
• Protects the antibodies against cleavage by guy enzymes

• IgG and IgM: blood
• IgG and monomeric IgA: extracellular fluid in tissues
• Dimeric IgA: secretions across epithelia, breast milk
• *note-fetus gets IgG from placental transport
• IgE: mast cells (allergic reactions)

• Binding of C11 to immune complex leads to binding of C4b and C3b which trigger CR1 on erythrocytes
• Erythrocytes transport the bound complexes to the liver and spleen where macrophages remove and destroy them

• 1. Cytotoxic T cells: recognize virus-derived peptides on MHC I
• 2. NK cells: invariant receptors recognize ligands that are induced on abnormal cells without the need for antibody
• 3. NK cells recognize/destroy antibody-coated target cells via antibody-dependent-cell-mediated cytotoxicity (ADCC)