Immunology – Chapter 3 Notes

K_d – measure of how strong a receptor binds its ligand (receptor-ligand interaction)

-            Otherwise known as affinity or dissociation constant

K_d = [S][L] / [SL]

-            Smaller K_d corresponds to stronger interaction between receptor and ligand

-            Lowest K_d 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