Lecture 22: Intro to Immunology Flashcards
Major components of innate immunity
- Complement
- Neutrophils
- Macrophages
- Innate Lymphoid Cells (e.g. NKs)
Activation pathways for complement
- Classical
- Alternative
- Lectin (mannose-binding)
Classical activation of complement
Mediated by antigen recognition via antibodies produced by B cells
Alternative activation of complement
Auto-destruction of anything that doesn’t inactivate C3
Lectin (mannose-binding) activation of complement
Recognition of foreign sugars on cell membranes
Opsonization
Tagging of pathogens by opsonins, allowing easy recognition + phagocytosis by mφ’s. Opsonin e.g. Abs, C3b, C4b
Neutrophils
- Innate immune cells born/stored as “marginal pools” in marrow.
- Released in circulation as adult and band cells.
- Enter CT via rolling adhesion/diapedesis, die after use.
- Utilize Pattern Recognition Receptors to recognize PAMPs/DAMPs.
- Capable of NETosis.
Macrophages
- Form as monocytes in marrow, then differentiate to mφ’s after diapedesis.
- Resident versions in peripheral tissues; mononuclear phagocyte system.
- Secondary roles in APCs, cell signaling.
Macrophage activation
Activated by inflammatory cytokines, can by hyperactivated by T cell cytokines. 2 activation modes:
1. Classical (M1)
2. Alternative (M2)
Classical activation of macrophages
Aka M1 macrophages, Type 1 inflammation, Th1 response. Phagocytic response.
Alternative activation of macrophages
Aka M2, Type II inflammation, Th2 response, immunoregulation response. Primarily used for tissue remodeling/repair; many varieties of a more subtle immune response.
Innate Lymphoid Cell groups
Group I: e.g. NK cells, IC pathogens
Group II: parasites, enriched in lung, skin, adipose
Group III: bacteria, fungi
Antibodies
- Aka Ag receptors/Ig/γ globulins.
- Can be soluble or membrane bound.
- Have variable Fab and constant Fc domains.
- 5 classes: IgG, IgD, IgA, IgM, IgE
Antibody structure
Variable Fab = heavy + light chain, antigen binding site, gives specificity (VDJ recombination)
Constant Fc = heavy chains, interacts with other immune components, defines antibody class/type.
Class switching
IgM is the default B cell antibody; upon activation, class switching can occur to other Ab types.
IgG
Most common Ab in blood/CT; readily diffusible. Triggers complement w/ sufficient Ag presence and can cross blood-placenta barrier for passive fetal immunity.
IgD
Not much known. Marker for mature naive B cells.
IgE
Mast cell surface receptor. Mediates parasite/allergy response by triggering degranulation.
IgM
IgG pentamer/hexamer; default Ab due to low immunogenicity. Multimeric structure requires more Ag density for activation but can bring multiple C1 proteins to activate complement; roles in early infection response.
IgA
Found in mucosal surfaces, breast milk. Dimer + “clip” structure gives acid resistance and can’t bind complement (clip blocks Fc); thus is important for Ag tolerance, esp. w/ food from gut.
B cell
EC pathogen response; expresses BCRs (Igs) which recognize Ags. Activates at critical Ag density; also req. B cell coreceptor complex/T cell signals/C3d to facilitate activation.
B cell life cycle
- Immature B cell leaves marrow.
- IgD/IgM expression defines mature naive B cell.
- Ag-dependent activation -> differentiation + clonal expansion to plasma cell.
- Potential class switching occurs + Ab secretion.
- Small Bmem population persists with Ab specificity.
T cells
IC pathogen response (viral, phagocytosed material). TCRs recognize MHC complexed Ag. Primarily classed as Tc or Th.
Tc cells
Cytotoxic T cells, CD8+. Self vs. non-self via MHC-1.
Th cells
Helper T cells, CD4+. Recognize internalized Ags from APCs complexed with MHC-II.
MHC-I
Expressed on almost all cells. Displays peptide fragments of produced proteins.
MHC-II
Expressed on APCs only. Displays peptide fragments from internalized proteins.
Other T cell types
Treg: CD4+ regulatory, immune suppression.
Tmem: CD4+ CD8+; central = self-renewing SCs, effector = CD8+ cytotoxic
γδ T cells: variant TCRs not MHC restricted; include intraepithelial lymphocytes.
Th subsets
Based on immune recruitment.
Th1 -> IFN-γ, TNF-α/β to help Tc vs IC viruses
Th2 -> IL-4/-5/-13 for B cell response vs worms, allergy
Th17 -> IL-6/-17 for mφ, neutrophil vs EC bacteria
Treg -> TGF-β, IL-10; dampen immune response.
Immune organ categories
Primary = generative (bone marrow, thymus)
Secondary = effector (peripheral MALT, lymph nodes, spleen, liver)
Thymus
Trains immunocompetence of immature T cells (thymocytes. Involutes with age to adipocytes. Derived from 3rd pharyngeal pouch endoderm; induction by ectomesenchyme/ectoderm interactions.
Blood-thymus barrier
ERCs physically block entrances to thymic medullar and reentry to circulation, keeping naive thymocytes trapped until immunocompetent.
DiGeorge syndrome
No thymus development; results in no T cells, no adaptive immunity
Thymic epithelial compartment
Cortex/medulla = epithelial-derived. Stroma formed by ERCs.
Epithelioreticular cells
Nurse/teacher cells for thymocytes; physically let out good thymocytes and trap immature ones.
Thymocyte pathway through spleen
- From vascular circulation -> perivascular -> epithelial for education
- Cortex -> medulla during education
- Medulla -> perivascular compartment -> vascular after immunocompetence
ERC classes
Type 1: cortical epithelioreticulum
Type 3: cortical/medullary border
Type 5: medullary
Type 6: assoc. w/ Hassall’s corpuscles
Thymic selection
- Positive selection (cortex; assure functional TCR that recognizes Ag; pre-req. for Th/Tc fate specification.
- Negative selection (medulla; assure non-self-reactive TCR; req. for access to perivascular space)
Non-immunocompetent cells are phagocytosed by thymic macrophages.
TCR development
- Naive: CD3- CD4- CD8-
- Double positive (cortex): CD3+ CD4+ CD8+
- Tc or Th (medulla): CD3+ CD4+/CD8+
What are thymoma disorders classed as?
Primary autoimmune disorders; failure in central tolerance.
B cell selection
Pos/neg selection of B cells occurs in marrow, preventing autoreactivity.
T cell exhaustion
During chronic active immune responses, gradual senescence of T cells to Tex occurs esp. for Tc/Tmem. Critical to chronic diseases.
Dendritic cell classes
- Conventional (mucosal surfaces)
- Plasmacytoid (blood, secondary immune organs; antiviral interferon secretion)
