Immunology Flashcards
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innate vs adaptive immune system
Innate:
- Physical barriers: epithelium (e.g., skin, mucous membranes)
- Secreted effector proteins and complement system
- Antigen-presenting cells, Natural killer cells, Granulocytes
- toll-like receptors (TLR): pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) and lead to activation of NF-kB
Adaptive:
- B cells, T cells (helper T cells, cytotoxic T cells)
- Immunoglobulins (IgA, IgM, IgG, IgD, IgE)
immune cell terminology
granulocytes:
mast cell, eosinophil, basophil, neutrophil
agranulocytes:
lymphocytes (NK cells, T-cells, B-cells), monocytes (–> macrophages)
immune cell lineage (from multipotential hematopoietic stem cell AKA hemocytoblast)
Common myeloid progenitor:
- megakaryocyte ==> thrombocytes
- erythrocytes
- myeloblasts ==> basophil, neutrophil, eosinophil, monocyte (–> macrophage)
Common lymphoid progenitor:
- natural killer cell (large granular lymphocyte)
- small lymphocyte ==> T-lymphocyte, B-lymphocyte (–> plasma cell)
cells of the innate immune system
monocytes/macrophages:
- monocytes (blood stream) become macrophages (tissues)
- phagocytosis, cytokine production, antigen presentation
- secrete pro-inflammatory cytokines: IL-1, TNF-a
neutrophils:
- provide extra support to macrophages
- phagocytosis only
- attracted by chemotaxins: IL-8, C5a
natural killer (NK) cells:
- kill infected human cells, produce IFN-y to activate macrophages
- destroy human cells with reduced MHC I
eosinophils, mast cells, basophils:
- contain granules with destructive enyzmes
- activated by IgE antibodies
- release of toxic substances to kill parasites
- mast cells in tissue, basophils in blood stream
respiratory burst (oxidative burst)
- part of innate immune system
- activation of the NADPH oxidase complex generates and releases ROS (free radicals) that destroy the pathogens in phagosomes
Pattern recognition receptors (PRRs)
- part of innate immune system
- recognize PAMPS (pathogen-associated moelcular patterns) and activate immune response
- Toll-like receptors (TLRs): activate the NF-κB pathway (proinflammatory cytokines, adhesion molecules) or IRFs (interferon regulatory factors, antiviral)
- Nucleotide-binding oligomerization domain-like receptors (NLRs): activation of NOD-like receptors → upregulation of NF-κB → ↑ transcription of proinflammatory cytokines (e.g., IL-1β, IL-18)
complement system
- can be activated by innate OR adaptive immune system
- amplifying cascade
-
alternative pathway, classical pathway, lectin pathway:
C3 ==> C3a (inflammation) ==> C3b (opsonization, phagocytosis) ==> C5a (inflammation) ==> C6-9 (MAC formation, lysis of microbe)
major functions of complement:
1. opsonization and phagocytosis
2. complement-mediated cytolysis (MAC)
3. stimulation of inflammatory reactions, destruction of microbes by leukocytes
cardinal signs of inflammation
- heat
- redness
- swelling
- pain
- loss of function
caused by a combination of vasodilation, vascular leakage, tissue damage
leukocyte extravasation (innate)
neutrophils
- rolling: leukocyte rolls along inner surface of vessel via binding of E-/P-selectin on endothelial cells
- crawling/arrest: tight binding of integrins with intercellular adhesion molecules (ICAM) on endothelial cells
- extravasation: diapedesis (passage of cell through blood vessel wall), transendothelial migration via binding of PECAM-1 between endothelial cells
- migration: leukocyte travels through interstitium to phagocytose foreign material
cytokines
- cell signaling proteins that stimulate inflammatory response
- chemokine: attracts immune cells (chemotaxis)
- interleukins (IL-1, IL-2): travel between leukocytes
- tumor necrosis factor (TNF): can cause tumor death
- transforming growth factor (TGF): repair
- interferons (Type I and II): Type I (alpha/beta) IFN interfere with viral replication, Type II (gamma) IFN activates macrophages
steps of phagocytosis
- engulfment
- phagosome acidification
- phagosome-lysosome fusion ==> phagolysosomes
- killing and digestion (ROS, NO, lysosomal enzymes)
MHC I and MCH II expressed by
MHC I: all nucleated cells
MHC II: only professional antigen-presenting cells (APCs)
- dendritic cells
- B lymphocytes
- macrophages
- thymic epithelial cells
MHC molecules bind only peptides
MHC molecules are membrane-bound
MHC I vs. MHC II
MHC I:
- originate from cytoplasmic proteins (Inside of cell)
- viral proteins ubiquitinated into peptides ==> peptides transported from cytoplasm into ER (TAP) where they are edited and loaded on MHC I ==> completed complex migrates to cell surface
- cross-presentation: endosomal antigens (usually MHC II) are secreted to cytoplasm –> MHC I pathway
MHC II:
- originate from extracellular proteins (phagocytosis by macrophages)
- lysosomal proteases degrade phagocytosed microbes into short papetides in phagolysosome ==> MHC II fuses with phagolysosome ==> completed complex migrates to cell surface
MHC and T cell relationship
CD8+ (cytotoxic) T cells = MHC I
CD4+ (helper) T cells = MHC II
1 x 8 = 2 x 4
- CD8+ T cells have 1 antigen-binding chain, have 1 letter after HLA (A, B, C)
- CD4+ T cells have 2 antigen-binding chains, have 2 letters after HLA (DP, DQ, DR)
diversity of antibodies and TCR
- DNA rearrangement/recombination of variable (V), diversity (D), joining (J) genes
–> recombinase activated gene (RAG) -
junction diversity: enzymes semi-randomly add and remove nucleotides at the ends of different gene segments
–> terminal deoxynucleotidyl transferase (TdT)
these genetically diverse regions encode the complementary determining region (CDR) loops involved in antigen recognition
CDR loops bind both MNC and peptide residues to TCR
