Antibody-Mediated Immunity: Development

• The learning objectives for the "Antibody-Mediated Immunity" lecture includes describing the development of prenatal immunity, understanding immune response changes through life, knowing immunoglobulin trends, mechanisms of antibody-mediated immunity, and contrasting T Cell and B Cell antigens.

Prenatal Immunity Development

• In weeks 4-6 of gestation, immune cells begin to form.
• Lymphoid organs (thymus, bone marrow, spleen, and lymph nodes) start developing in weeks 8-12.
• Between 12-20 weeks, the immune system produces B cells, which mature in the bone marrow, and T cells, which mature in the thymus.
• Close to 28 weeks and right before birth, the fetus receives the majority of IgG antibodies from the mother via the placenta, providing crucial passive immunity.
• At birth and with first exposure to bacteria, the baby's immune system gets stimulated for the first time.
• B cells first appear in the fetal liver and bone marrow by week 8.
• Immunoglobulins are detectable from weeks 10-30 in the order: IgM > IgD > IgG > IgA.
• Maternal IgG antibody transfer begins by week 16; 50% is transferred by the 34th week.
• Breastfeeding provides extra immunity via colostrum, which contains IgA antibodies and other immune-supporting factors.

Immune Response Through Life

• In neonates, the immune system is present but underdeveloped, producing all immunoglobulin types with IgM dominating and maternal IgG lasting up to 6 months.
• During childhood, common acute infections and routine immunizations occur, with immune responses maturing around 2-3 years old.
• In adolescence, environmental factors (culture, geography, socioeconomic status, nutrition), along with physical and emotional puberty, affect immunity.
• During adulthood, the immune system is well-developed and experiences, contracting 2-5 common acute infections yearly, and the thymus reduces significantly by ages 40-45.
• In geriatric individuals, biological age variation affects immunity, depending on activity levels, genetics, diet, and health conditions.

Immunoglobulin Levels

• Newborns receive passive immunity from their mothers, which decreases until 6 months of age, after which the infant's own immunoglobulin levels will increase up until adulthood, where it reaches its maximum levels.

Antibody-Mediated Immunity Mechanisms

• Neutralization blocks viruses and toxins by using antibodies to stick to them, stopping the spread.
• Opsonization marks antigens so they can be easily found and destroyed, where antibodies attach to the antigen for recognition and engulfment by immune cells such as macrophages.
• Complement fixation is a process that employs a backup group of proteins to help destroy an antigen, by creating holes in an antigen's outer shell, causing it to leak and die.

T Cell vs. B Cell Antigens

• B cell antigens respond to, and directly bind to, intact antigens, which can be aided by T cells; they also produce antibodies to mark antigens, deal with free-floating antigens, and form memory cells.
• T cell antigens respond to processed antigens presented by MHC, can directly kill infected cells, and form memory cells.
• B cells recognizes the entire antigen and produce antibodies to neutralize them.
• T cells recognize processed antigens and take action directly or indirectly.

T Cell and B Cell Receptors

• B Cell receptors are "Y" shaped, with variable regions at the top that bind to antigens; they are triggered to produce more antibodies upon binding.
• T cell receptors have two parallel lines, with a variable region at the top that binds to antigen fragments and triggers T cell action.

T Cell Surface Molecules

• CD3 is found on all T cells and sends activation signals when the T cell recognizes an antigen.
• CD4 is mostly found on helper T cells (Th cells) and helps recognize signals from antigen-presenting cells, while also directing the immune response by activating cells like B cells.
• CD8 is mostly found on cytotoxic T cells (Tc cells) and helps recognize and kill infected or cancerous cells.

T Cell Negative Selection

• Negative selection removes dangerous T cells that mistakenly attack healthy cells.
• T cells mature in the thymus and learn to recognize threats with "self-testing" cells that show T cells pieces of normal proteins.
• If a T cell reacts too strongly to the body's own proteins, it is killed off, which prevents autoimmune diseases.
• The T cells that don't overreact continue to be part of the immune system.

T Cell Positive Selection

• Positive selection teaches T cells to recognize threats correctly and ensures survival of functional T cells able to recognize the body's MHC system.
• T cells arrive in the thymus as immature cells, where cortical thymic epithelial cells (cTECs) show the T cells tiny protein fragments with MHC molecules.
• T cells that correctly recognize MHC receive a survival signal, while those that don't die off.
• A T cell that binds to MHC class I becomes a CD8+ (cytotoxic) T cell or if it binds to MHC class II, it becomes a CD4+ (helper) T cell.

T Cell Development Stages

• The double negative (DN) stage is where T cells start as "blank slates," expressing CD2, CD5, and CD7, with low CD3 levels.
• The double positive (DP) stage occurs after early selection and express both CD4 and CD8.
• At the single positive (SP) stage, T cells differentiate into CD4+ (helper) or CD8+ (cytotoxic) cells, with fully present CD3.
• Mature T Cells are fully trained CD4+ or CD8+ T cells that circulate in the blood and are ready to fight infections.

T Cell Development Terms

• The terms "double negative” and “double positive” help track the step-by-step transformation of T cells as they mature.

T Cell Receptor (TCR)

• A TCR is made of two protein chains (α & β chains) that binds to small antigen pieces presented by MHC molecules and acts as a key fitting into a lock with MHC and antigen.
• The CD3 Complex helps transmit signals when the TCR binds to an antigen.
• Co-receptors like CD4 or CD8 help the TCR recognize whether the antigen is coming from MHC class I or II.
• The molecule, CD28, strengthens activation signals.
• The most common TCR type is αβ TCR (Alpha-Beta TCR), made of one alpha (a) chain and one beta (β) chain, which recognizes antigens presented by MHC molecules
• The γδ TCR (Gamma-Delta TCR) is found on a smaller subset of T cells in the gut, skin, and mucosal tissues that recognizes antigens without MHC molecules and is important for tissue repair, cancer surveillance, and early infection.
• A TCR signals as an alarm system that triggers activation when it binds to an antigen on an MHC molecule, which because the TCR cannot signal without assistance, the CD3 complex transmits its signals.
• Cellular components involved in T Cell signal transduction include TCR, CD3 complex, and Co-receptors (CD4 and CD8).
• Co-stimulation involves two signals to activate T cells, ensuring correct immune response and protection of the body’s own cells, to prevent T cells from attacking healthy cells, help activate T cells properly, and regulate T cells from over/underreacting.
• MHC Class I presents pieces from inside the cell to CD8+ T cells, while MHC Class II presents pieces from outside the cell to CD4+ T cells.

T Cell Receptor Binding

• Once an antigen is presented on MHC, a T cell checks it using its T cell receptor (TCR), acting like a key trying to fit into a lock.

Superantigens

• Superantigens are a type of antigen that bypasses the normal TCR and MHC matching process; instead, it directly binds to trigger a massive T cell activation.
• Leads to the uncontrolled immune response, overproduction of cytokines, and dysregulation of immune response.
• Profound immunostimulation means the immune system is in overload, while profound paradoxical immunosuppression means the immune system collapses from being overloaded.

MHC Classes

• MHC Class I and Cytotoxic T Cells (CD8+ T Cells) are found on all body cells, presents antigens from inside, and interacts with CD8+ T cells.
• MHC Class II and Helper T Cells (CD4+ T Cells) are found only on antigen-presenting cells, presents antigens from outside the cell, and interacts with CD4+ T Cells.
• Cytotoxic T Cell (CD8+) antigen processing includes using MHC Class I to fight threats inside cells, triggering infected cell destruction to stop the spread of virus, upon a virus infecting it.
• Helper T Cell (CD4+) antigen processing includes fighting threats outside cells using MHC Class II; where antigen presenting cells engulf and degrade bacteria, presenting peptides which then helper T cells come to scan MHC class II to check for threats.
• Steps for an antigen-presenting cell (APC) to activate a T Cell are that the APC processes antigen, then breaks down antigen and loads it onto an MHC class, and if it’s a Naive T Cell that recognizes and binds to an T Cell receptor, the APC releases cytokines and presents a second activation signal, the T cell is activated to release cytokines.

T-Cell Checkpoints

• T Cell checkpoints are molecules that function to prevent the immune system from attacking the body by mistake.
• In cancer immunity, cancer cells can express checkpoint proteins that can signal T cells to become ineffective at attacking cancer cells.
• Naive T Cells are those that have never encountered an antigen
• Mature T Cells have gone through training, are well developed, and are capable of recognizing and responding to antigens.

Helper T Cells

• Helper T (Th) Cells organize and direct the immune response.
• Cytotoxic T (Cytotoxic T Lymphocyte - CTL) Cells find and destroy infected cells.
• Helper T (Th) cells have CD4 as their surface markers and this helps Th cells recognize and bind to MHC Class II molecules on Antigen-Presenting Cells (APCs).
• Cytotoxic T (CTL) Cells have CD8 as their surface markers and this allows cytotoxic T cells to recognize and bind to MHC Class I molecules on infected or abnormal cells;
• Th1 activates cytotoxic T cells to fight viruses & intracellular bacteria.
• Th2 activates B cells and eosinophils to fight parasites & allergens.
• Th17 helps fight fungi and bacteria, can cause inflammation.
• Tfh helps B cells make better antibodies.
• Treg calms down the immune system to prevent autoimmune diseases.
• Th1 Cells produce IFN-γ (Interferon-gamma), which activates macrophages to kill intracellular bacteria and viruses.
• Th2 cells uses IL-4 which helps B cells produce antibodies for fighting parasites and allergic responses.
• Th17 cells use IL-17 which stimulates neutrophils to frontline immune cells that attack bacteria and fungi.
• Tfh Cells are directed at any pathogen that requires long-term immunity
• Treg uses TGF-ẞ and IL-10 which are directed at autoimmune diseases
• T cells capture a pathogen, breaks it down, and presents it to Tho-based pathogen detection which releases cytokines that tell the Tho cell what kind of Th cell it should become to take it’s place
• A treg slows down the immune response to prevent to autoimmunity
• "Ordinary T helper cell speeds up the immune response to fight infections.
• Treg cells specifically express to their immunosuppressive development to differentiate from activated cells
• Follicular T helper (Tfh are at lymphoid follicles
• ordinary T helper cells are at the spleen
• "Ordinary T helper cells help destroy infected cells,
• IL.21/IL-4 help follicular T cells to destroy a particular cytokine
• A Cytotoxic T Lymphocyte scanner the Tcell and releases molecules of infection preventing the infection from spreading

Lymphocyte Mechanisms

• Perforin punches holes in the infected cell's and slip through and trigger apoptosis to trigger death to not kill it’s system
• A APC creates a cell that presents a piece of antigen to the APC APC releases cytokines that make the CTL mature
• ydC. have receptors that allow for broader antigens that don't require presentation from MHC
• NK cells use a balance between activating and killing the cell in cancerous ones
• Antibodies are killed by presence a a bridge between a cell without an antigen present.

Inflammation Notes

• Inflammation is the response of vascularized tissue to injury or infection
• Macrophages initiate an inflammatory response
• Proinflammatory cytokines make
• and Neutrophils interact with the endothelium
• 3 mechanisms activate with corticosteroids to inhibit activity and production
• Cortecosteroids affect inflammation
• to treat rheumatoid and psoriasis
• targets can block signaling which is used for arthritis
• inhibitors help treat colitic diseases 0
• cbn reduce polarization toward pro-inflammatory
• cb1 affect inflammation when polarize
• the receptors that the cb2 make help reduce inflammation , they're are being investigated for diseases

Lectures

• Provides protection at mucosal surfaces of tracts (GI, respiratory, and genitourinary) that secrete to protect from pathogens,
• Lymphocites are at five locations:
• Waldeyer's Ring
• peyer's patches
• folliciles
• laming propria
• lyphocites
• Non-specific and specific factors work together to project that are mainly found at the gut, protect the body
• Mucous membrane is the one focus on the body
• IgA antibodies
• t-cells are used that infect in the immune
• immunoglobulins that are regulated by T-CELLS
• T- Cells the help cells produce the antibody
• When a pathogen enters an antibody they will
• The transport across epithelium across the body
• transfer is an protection infection in the womb
• Transfer of AIG in birth
• Immunity in the systems are less vulnerable and prone to infectious systems

Breastmilk Notes

• There are many different types of immune proteins that transfer through breastmilk.
• Breastmilk produces protein and signalling molecules that reduce infectious responses.
• dietary and environmental are absorbed by the antibodies that are passed down to the babies
• breast milk as enzymes, is lactose, and has antiviral lipids that can heal the fetus

Lecture

• The cytokines communicate that are both powerful and signal through the bloodstream
• a protein that travels and binds to different cells and activates them depending on the cell

Cytocines

• fights bacterias and viruses in the cell

• fight parasites and trigger cells

• activate immune cells

• Cytokines calm prevent cells from reacting

• that helps with tissue destruction

• they function relate to the structure of the cell

• can bind and move cells

• different chemokines receptors that release signals and also only to a main signal

Lecture

• act like signals to attract the inflammation and
• help immune support
• help different cells boost their defences and make it hard to cells from spreading Primary function of CSFs is to stimmulate and is the periphary of the immune signal G helps granuloma and stimmalte, activate and help the immune cell and help a blood vessel and support immune cells
• basic function and recpror to send signals.
• The cyokines will cause different reactiions based depending on the person to cause pharmacies to affect people.