Janeway's Immunobiology

Tuesday, August 11, 2020 13:14

Principles of Innate Immunity

o Pathogens
○ Viruses (5-100s nm)
§ Directly kill cells by inducing lysis during replication
○ Bacteria & Mycobacteria
§ Directly kill cells or damage cells by producing toxins
○ Fungi
○ Parasites
§ Plasmodium genus - cause Malaria
□ Directly kill infected cells
§ Parasitic worms (helminths)
□ Too large to infect host cells but can injure tissues by forming cysts that
induce damaging cellular responses
§ Extracellular
□ Induce shock and sepsis by releasing toxins into blood or tissues
o Avoidance, Resistance and Tolerance
o Complement
○ Acts with antibodies to lyse bacteria
○ ~ 30 plasma proteins that act together
○ Can also target foreign organisms w/o a specific antibody-- cont. to innate and adaptive
responses
o Activation of immune system
○ Inflammatory inducers
§ Molecular components unique to bacteria or viruses
□ Bacterial lipopolysaccharides or molecules like ATP
○ Detected by Sensor Cells
o Innate immune system
○ Common Myeloid Progenitor (CMP) is precursor of
§ Macrophages
□ In almost all tissues
□ Monocytes mature into macrophages (monocytes are in blood)
□ Disposes of garbage for innate, adaptive and just day-to-day cell life
□ Also help induce inflammation
§ Granulocytes (WBC) don't live very long
□ Neutrophils
® Phagocytose and activate bactericidal mechanisms
□ Eosinophils & Basophils
® E -> Kills antibody-coated parasites
® Mostly anti-parasites b/c the're too big to be engulfed
® These guys will just release bunches of enzymes and toxic proteins
§ Mast cells
□ Full of inflammatory mediators (histamine & proteases) -> protect skin,
intestines and airway from parasitic worms
 □ Eosinophils & Basophils
® E -> Kills antibody-coated parasites
® Mostly anti-parasites b/c the're too big to be engulfed
® These guys will just release bunches of enzymes and toxic proteins
§ Mast cells
□ Full of inflammatory mediators (histamine & proteases) -> protect skin,
intestines and airway from parasitic worms
§ Dendritic Cells
□ Do micropinocytosis but mainly they are sensor cells that produce other
mediators -- they specifically activate T-lymphocytes of he adaptive
immune system
§ (Also is precursor of megakaryocytes and red blood cells)
○ Just proteins alone did not create a strong immune response. You needed microbes as
well like killed bacteria or stuff from bacteria
§ Adjuvant -> helped intensify the response to the immunizing antigen
○ The sensor cells (macrophages, neutrophils, and dendritic cells)
§ Have PRR: pattern-recognition receptors
□ Toll-like receptors
® Transmembrane, detect extracellular bacteria
□ NOD-like receptors
® Sense intracellular bacterial invasion
§ Recognize PAMPS: pathogen-associated molecular patterns
□ Oligosaccharides, peptidoglycans and libopolysaccharides of the bacterial
cell wall
□ Unmethylated CpG DNA => loads of pathogens have this
§ Can also detect diff in
□ Host mRNA and bacterial RNA and host and microbial DNA
§ Also cellular damage induced by pathogens and maybe not even the actual
pathogens idk it's very confusing
§ The PRRs can either
□ Induce the effector functions in the cells (phagocytosis and degredation)
□ Release inflammatory mediators to amplify the immune response
○ Sensor cells produce mediators (proteins that act similarly to hormones!!!)
§ Cytokines
□ Name for anything secreted by immune cell that impacts behavior of close-
by cells that detect them by receptor
□ Usually ends up amplifying the effector function of the target cell
§ Chemokines ` marshalls'
□ "Chemoattractants" to attract cells that have chemokine receptors to the
infected tissue
§ Inflammation
□ Recruit cells from the blood into the infected tissues
□ Increases lymph flow
® Takes Antigens (either the pathogen itself or an APC to lymphoid
tissue
○ Common Lymphoid Progenitor (CLP) in bone marrow gives rise to antigen-specific
§ Innate Lymphoid Cells (ILCs) - In the peripheral tissues like the intestines
□ Natural killer (NK) cells
® Lack antigen-specificity but can kill tumor cells and others
o Adaptive Immune System
○ B Lymphocytes
§ B-cell antigen receptor
□ Encoded by same genes that encode antibodies (Ig)
□ Called mIg or sIg
 □ Natural killer (NK) cells
® Lack antigen-specificity but can kill tumor cells and others
o Adaptive Immune System
○ B Lymphocytes
§ B-cell antigen receptor
□ Encoded by same genes that encode antibodies (Ig)
□ Called mIg or sIg
§ Plasma cell
□ Effector form of B-cell -> after antigen binds to B-cell receptor
□ Create ANTIBODIES that have same specificity as the B-cell receptor of
plasma cell
○ T Lymphocytes
§ T-cell antigen receptor (TCR)
§ Effector T-cells - after the T-cell encounters an antigen
□ Cytotoxic T-cells
® Kill cells that bear the antigen
□ Helper T-cells
® Provides signals - specific cytokines that activate the functions of
other cells ~ B cell prod of antibodies and macrophages killing
engulfed pathogens
□ Regulatory T-cells
® Suppress the activity of other lymphocytes & limit damage of
immune responses
○ Memory cells
§ B and T cells activated by antigen and that can readily differentiate into effector
cells on second exposure to the antigen
o Antibodies & T-cell Receptor Structure
○ Antibodies
§ Fc Region (constant region)
□ Takes on 4-5 distinguishable formats
□ Effector function (has this)
§ Fv Region (fragment variable
□ Antigen binding site to determine antigen binding specificity of Ab
molecule
§ T-cell Receptors
□ Made up of alpha and beta chains
○ Epitope Recognition by
§ Antibody
□ Proteins, glycoproteins and polysaccharides of pathogens (normally)
□ Can really recognize anything, but the above are most common
§ T-cell Receptor
□ Depend on antigen breakdown first (by proteases)
□ Depend on peptide fragment binding to MHC molecules for recognition
□ Just signal to T cell that it has bound its antigen
o Antigen-receptor genes
○ Unlike the sensor cells in the innate immune system, which detect a finite number of
stimuli, the antigen-specific receptors detect a seemingly infinite range of epitopes, but
are encoded by finite number of genes.
○ Combinatorial diversity
§ IgG Fv regions are encoded as a sets of discrete gene segments
§ During B cell development in bone marrow & T-cell receptor development in the
thymus, these gene segments are joined by DNA recombination to form a
complete variable region
 stimuli, the antigen-specific receptors detect a seemingly infinite range of epitopes, but
are encoded by finite number of genes.
○ Combinatorial diversity
§ IgG Fv regions are encoded as a sets of discrete gene segments
§ During B cell development in bone marrow & T-cell receptor development in the
thymus, these gene segments are joined by DNA recombination to form a
complete variable region
○ Junctional diversity
§ Random addition or subtraction of nucleotides at the junctions of gene segments
○ Unlike in innate immunity, lymphocytes have the only one type of receptor. For innate
immunity receptors on those cells can sense many different types of pathogens
o Clonal Selection Hypothesis
○ Each lymphocyte has one type of receptor
○ Interaction between foreign antigen and lymphocyte receptor leads to lymphocyte
activation
○ Differentiated cells will bear receptors of identical specificity to those of the parental cell
from which the lymphocyte was derived
○ Clonal Deletion -> Lymphocytes that have receptors specific to ubiquitous self molecules
are deleted at an early stage of development and do not become mature lymphocytes
o Lymphoid Tissues and Organs
○ Central/Primary Lymphoid Organs
§ Bone Marrow (B & T Lymphocytes)
§ Thymus
○ Peripheral/Secondary Lymphoid Organs
§ Lymph Nodes
§ Spleen
□ Has no connection with the lymphatic system. Collects antigens and
lymphocytes straight from blood
□ Red Pulp -> site of red blood cell disposal
§ Mucosal lymphoid tissue of gut, nasal, respiratory, urogenital and other mucos
□ Mucosa
o Antigen Presenting Cells in peripheral lymphoid organs
○ Activation of PRR on dendritic cells triggers presentation of antigens on MHC molecules
and expression of co-stimulatory molecules which help T lymphocytes to proliferate and
differentiate into final form