Chapter 3 - Recognition and Response
Immunology – Chapter 3 Notes
Kd – measure of how strong a receptor binds its ligand (receptor-ligand interaction)
- Otherwise known as affinity or dissociation constant
Kd = [S][L] / [SL]
- Smaller Kd corresponds to stronger interaction between receptor and ligand
- Lowest Kd is about 10-12 M (avg. is about 10-5 M)
- [S]: Substrate conc.
- [L]: Ligand conc.
- [SL]: Substrate/Ligand complex conc.
Multivalent binding: ligand can have interactions with multiple receptors at once (ex. bivalent)
- Related to Avidity (the ability of multivalent receptors and ligands to hold an interaction, or the overall strength of a reaction, could be through more than one interaction)
- Because of the fluid mosaic membrane model, receptors can form clusters with a ligand by moving around the membrane
- This mechanism is also used between T-helper cells and antigen presenting cells to form a close association for communication and alert of cytotoxic T-cells with cytokines
Generation of Diversity
- DNA Recombination plays a major role in generation of diversity receptors on B and T cells
- Mixing or complexing of multiple different receptors (ex. alpha and beta receptors) creates combinatorial enhanced affinity with ligands (can happen multiple times with many unique receptors)
B-Cell Receptors (BCR)
- Function like a handshake with ligands
- Has a hydrophobic section with a small cytosolic segment, and a spacer on the membrane bound form
- The secreted form (3Dprinted hand) has only a small hydrophilic end
- B-cell receptors can be secreted, while T-cell receptors cannot
Antibody Structure:
- Have heavy and light chains with varied forms
- V and C major types with H and L subscripts
- V: variable
o Only the 4 ends, even within the same antibody class, are highly variable
- C: constant
- L or H stand for light or heavy chain protein
- There is about ½ variable acids in light chain versus about ¼ in heavy chain
- Variable regions are close to N-terminus, while Constant regions are to the C-terminus
o One of the reasons it is variable and on the end is so that it can bind antigens
- Hinge region: has disulfide bonds from cysteine residues
- Light chain region only has two chain types for the constant region, making only 3 possible combinations
o Greek characters kappa and lambda
- Heavy chain region has mew, gamma, alpha, delta, or epsilon constants
o Creates many possible combinations in different positions
- Complementary Determining Region (CDRs): CDR3 is the most variable region in both the heavy and light chain, while other CDRs are less variable in different forms of Ig
- Has a carbohydrate side chain to facilitate solubility of the antibody
-
-
Immunoglobulin
- Characterized by CDRs
- IgG, IgM, IgA, IgD, IgE
- Hinge regions are observed in IgG, IgD, and IgA
- Dimers are observed in IgA connected to a J-chain
- Pentamers can be observed in IgM around a J-chain
- J-chain is a polypeptide with disulfide linkages
- Each Ig has subtypes
-
- IgG1 to IgG4, with IgG3 being the longest C-chain
-
- Learn the chart lol
B-cell receptors:
- Immature B-cells only have IgM
- Mature (naïve) B-cells express both IgM and IgD
- Activated B-cells again express only IgM
- ITAMs: Immunoreceptor Tyrosine-Based Activation Motifs which can be phosphorylated to activate B-cells
o Present in both B and T cells
o Made up by Ig(alpha) and Ig(beta) dimer
- CD21 directly associates with C3d, which is part of the complement system
o C3d, serves as a marker that sticks to antigens and brings them to B-cell receptor antibodies
o Also known as the B-cell coreceptor
-
T-cell receptors:
- bruh I don’t know what’s supposed to go here apparently I missed it in class lol
Know Table 3.1 on page 211 – receptors and ligands
Cancer has two paths:
- Evade: PD1 – PdL1
- Immune-modulation
Chemotaxis: anything that causes movement in response to stimulus
T-cell interaction with dendritic cells:
- CD28 interacts with CD80 or CD86 on the dendritic cell
- CD4 guides MHCII to the TCR
- There are 3 heterodimer pairs of CD3 surrounding the TCR
o Which heterodimer pair has more phosphorylation sites?
o The Z pair has three
-
Innate Immune Cell Receptors:
- PRR secrete cytokines which activate T and B cells which secrete cytokines
- Can be found either membrane bound or cytoplasmic (ex. covid)
- Clonal: refers to “one type,” esp. in cell receptors
o Displayed in all cells that encounter antigens, ex. innate immune cells (macrophages, natural killer cells), mucous cells, epithelial, keratinocytes
o These cells can change roles from fighting to becoming messenger cells
- Pathogen Associated Molecular Patterns
o Microbe (MAMP)
o Damage (DAMP)
o Know Table 3-2 Names and Locations
o
Cytokine Receptors:
- Assist locomotion, increase or decrease activity of particular enzymes, change transcription, direct cell death
- Cytokines have strong affinity (Kd 10^-8 – 10^-12) to their receptors
- Small number of cytokines can have a large effect due to affinity and proximity
- Know the 6 classes of cytokines and their functions (3-3)
-
- Interleukin (IL) discovered first – named for inter communication between leukocytes
o Endocrine: enter bloodstream and affect entire body
o Paracrine: direct vicinity
o Autocrine: affect self
- Pleiotropic cytokines: one can affect multiple different target cells
- Redundant cytokines: multiple cytokines have similar function
o A pleiotropic cytokine can also be redundant (similar to immuno class)
- Synergy: additive cytokine response
- Antagonism: one cytokine response inhibits the effect of another
- Cascade induction: cytokine response creates more cytokines which repeats
- Know the technical problems in cytokine therapy (pg. 228)
o It is difficult to achieve a high concentration of cytokines in a specific area artificially through injection or ingestion
o Need to be stabilized before body, but also destabilized in the body
o Can elicit too much response from leukocytes leaving other parts of the body vulnerable
Cytokine families
- Regarding individual cytokines, need to know the name (IL-1,10,2, etc.), secreted by C cells (which cells?), targets C cells (which cells?), overall function (inflammation, growth, etc.), any relevant extra information
- IL-1 family:
o IL-1 a/B, IL-18, IL-33, IL-1Ra
o Intermediate between innate and adaptive immune systems
o Secreted by innate immune cells (monocytes, dendritic cells, etc.)
o Target adaptive B and T cells, and other cytokine-secreting cells
o Activate adaptive immune response
o Caspase-1 causes cytokines to mature and be activated
o IL-1 binds IL-1RI receptor, which causes an immune response
o IL-1Ra: “mimic ligand” of IL-1 and binds the IL-1RI and II receptors without causing immune response (inhibitory)
- Know the 3 subgroups of IL in table 3-4
- Class 1 (hematopoietic) family:
- IL-2: functions in B and T cell proliferation ?
- IL-4: targets T-helper cells
- Class 2 Cytokines: (interferons)
o 3 subtypes – alpha and beta (type 1), gamma (type 2), lambda (type 3)
o Type 1: Secreted when a PRR encounters PAMP, ribonuclease
o Type 2: ribonucleases
§ Exhibit ribonuclease activity to kill RNA and stop viral infection
§ Clinically used (ex. leprosy), but type 1 can exhibit same property
o Type 3:
- TNF (tumor necrosis family):
o TNF alpha, beta, etc.
o Functions in promoting inflammation in various cells
o Usually secreted by activated macrophages, lymphocytes, fibroblasts, and keratinocytes
o Increases expression of MHC glycoproteins
o When TNF binds TNF receptor-1 molecules, they form a trimer and cause intracellular response
o Decoy receptors: non-membrane bound, soluble TNF receptors that bind TNF and therefore do not cause response (inhibitory)
- IL-17 family:
o Secreted by T-helper cells
o Know from table that they are named IL-17A through IL-17F
There are disulfide linkages and naming system in table
Immunology – Chapter 3 Notes
Kd – measure of how strong a receptor binds its ligand (receptor-ligand interaction)
- Otherwise known as affinity or dissociation constant
Kd = [S][L] / [SL]
- Smaller Kd corresponds to stronger interaction between receptor and ligand
- Lowest Kd is about 10-12 M (avg. is about 10-5 M)
- [S]: Substrate conc.
- [L]: Ligand conc.
- [SL]: Substrate/Ligand complex conc.
Multivalent binding: ligand can have interactions with multiple receptors at once (ex. bivalent)
- Related to Avidity (the ability of multivalent receptors and ligands to hold an interaction, or the overall strength of a reaction, could be through more than one interaction)
- Because of the fluid mosaic membrane model, receptors can form clusters with a ligand by moving around the membrane
- This mechanism is also used between T-helper cells and antigen presenting cells to form a close association for communication and alert of cytotoxic T-cells with cytokines
Generation of Diversity
- DNA Recombination plays a major role in generation of diversity receptors on B and T cells
- Mixing or complexing of multiple different receptors (ex. alpha and beta receptors) creates combinatorial enhanced affinity with ligands (can happen multiple times with many unique receptors)
B-Cell Receptors (BCR)
- Function like a handshake with ligands
- Has a hydrophobic section with a small cytosolic segment, and a spacer on the membrane bound form
- The secreted form (3Dprinted hand) has only a small hydrophilic end
- B-cell receptors can be secreted, while T-cell receptors cannot
Antibody Structure:
- Have heavy and light chains with varied forms
- V and C major types with H and L subscripts
- V: variable
o Only the 4 ends, even within the same antibody class, are highly variable
- C: constant
- L or H stand for light or heavy chain protein
- There is about ½ variable acids in light chain versus about ¼ in heavy chain
- Variable regions are close to N-terminus, while Constant regions are to the C-terminus
o One of the reasons it is variable and on the end is so that it can bind antigens
- Hinge region: has disulfide bonds from cysteine residues
- Light chain region only has two chain types for the constant region, making only 3 possible combinations
o Greek characters kappa and lambda
- Heavy chain region has mew, gamma, alpha, delta, or epsilon constants
o Creates many possible combinations in different positions
- Complementary Determining Region (CDRs): CDR3 is the most variable region in both the heavy and light chain, while other CDRs are less variable in different forms of Ig
- Has a carbohydrate side chain to facilitate solubility of the antibody
-
-
Immunoglobulin
- Characterized by CDRs
- IgG, IgM, IgA, IgD, IgE
- Hinge regions are observed in IgG, IgD, and IgA
- Dimers are observed in IgA connected to a J-chain
- Pentamers can be observed in IgM around a J-chain
- J-chain is a polypeptide with disulfide linkages
- Each Ig has subtypes
-
- IgG1 to IgG4, with IgG3 being the longest C-chain
-
- Learn the chart lol
B-cell receptors:
- Immature B-cells only have IgM
- Mature (naïve) B-cells express both IgM and IgD
- Activated B-cells again express only IgM
- ITAMs: Immunoreceptor Tyrosine-Based Activation Motifs which can be phosphorylated to activate B-cells
o Present in both B and T cells
o Made up by Ig(alpha) and Ig(beta) dimer
- CD21 directly associates with C3d, which is part of the complement system
o C3d, serves as a marker that sticks to antigens and brings them to B-cell receptor antibodies
o Also known as the B-cell coreceptor
-
T-cell receptors:
- bruh I don’t know what’s supposed to go here apparently I missed it in class lol
Know Table 3.1 on page 211 – receptors and ligands
Cancer has two paths:
- Evade: PD1 – PdL1
- Immune-modulation
Chemotaxis: anything that causes movement in response to stimulus
T-cell interaction with dendritic cells:
- CD28 interacts with CD80 or CD86 on the dendritic cell
- CD4 guides MHCII to the TCR
- There are 3 heterodimer pairs of CD3 surrounding the TCR
o Which heterodimer pair has more phosphorylation sites?
o The Z pair has three
-
Innate Immune Cell Receptors:
- PRR secrete cytokines which activate T and B cells which secrete cytokines
- Can be found either membrane bound or cytoplasmic (ex. covid)
- Clonal: refers to “one type,” esp. in cell receptors
o Displayed in all cells that encounter antigens, ex. innate immune cells (macrophages, natural killer cells), mucous cells, epithelial, keratinocytes
o These cells can change roles from fighting to becoming messenger cells
- Pathogen Associated Molecular Patterns
o Microbe (MAMP)
o Damage (DAMP)
o Know Table 3-2 Names and Locations
o
Cytokine Receptors:
- Assist locomotion, increase or decrease activity of particular enzymes, change transcription, direct cell death
- Cytokines have strong affinity (Kd 10^-8 – 10^-12) to their receptors
- Small number of cytokines can have a large effect due to affinity and proximity
- Know the 6 classes of cytokines and their functions (3-3)
-
- Interleukin (IL) discovered first – named for inter communication between leukocytes
o Endocrine: enter bloodstream and affect entire body
o Paracrine: direct vicinity
o Autocrine: affect self
- Pleiotropic cytokines: one can affect multiple different target cells
- Redundant cytokines: multiple cytokines have similar function
o A pleiotropic cytokine can also be redundant (similar to immuno class)
- Synergy: additive cytokine response
- Antagonism: one cytokine response inhibits the effect of another
- Cascade induction: cytokine response creates more cytokines which repeats
- Know the technical problems in cytokine therapy (pg. 228)
o It is difficult to achieve a high concentration of cytokines in a specific area artificially through injection or ingestion
o Need to be stabilized before body, but also destabilized in the body
o Can elicit too much response from leukocytes leaving other parts of the body vulnerable
Cytokine families
- Regarding individual cytokines, need to know the name (IL-1,10,2, etc.), secreted by C cells (which cells?), targets C cells (which cells?), overall function (inflammation, growth, etc.), any relevant extra information
- IL-1 family:
o IL-1 a/B, IL-18, IL-33, IL-1Ra
o Intermediate between innate and adaptive immune systems
o Secreted by innate immune cells (monocytes, dendritic cells, etc.)
o Target adaptive B and T cells, and other cytokine-secreting cells
o Activate adaptive immune response
o Caspase-1 causes cytokines to mature and be activated
o IL-1 binds IL-1RI receptor, which causes an immune response
o IL-1Ra: “mimic ligand” of IL-1 and binds the IL-1RI and II receptors without causing immune response (inhibitory)
- Know the 3 subgroups of IL in table 3-4
- Class 1 (hematopoietic) family:
- IL-2: functions in B and T cell proliferation ?
- IL-4: targets T-helper cells
- Class 2 Cytokines: (interferons)
o 3 subtypes – alpha and beta (type 1), gamma (type 2), lambda (type 3)
o Type 1: Secreted when a PRR encounters PAMP, ribonuclease
o Type 2: ribonucleases
§ Exhibit ribonuclease activity to kill RNA and stop viral infection
§ Clinically used (ex. leprosy), but type 1 can exhibit same property
o Type 3:
- TNF (tumor necrosis family):
o TNF alpha, beta, etc.
o Functions in promoting inflammation in various cells
o Usually secreted by activated macrophages, lymphocytes, fibroblasts, and keratinocytes
o Increases expression of MHC glycoproteins
o When TNF binds TNF receptor-1 molecules, they form a trimer and cause intracellular response
o Decoy receptors: non-membrane bound, soluble TNF receptors that bind TNF and therefore do not cause response (inhibitory)
- IL-17 family:
o Secreted by T-helper cells
o Know from table that they are named IL-17A through IL-17F
There are disulfide linkages and naming system in table
