Understanding the Immune System

• The immune system comprises organs, cells, and molecules collaborating to protect against microorganisms.
• It features two main branches: the innate and adaptive immune responses.

Innate Immune Response

• Non-specific cells differentiate invaders from human cells, but not between different invaders.
• It is a rapid response system without immunological memory.
• It responds identically to a pathogen regardless of prior encounters.

Adaptive Immune Response

• Specific to viruses and bacteria, it identifies pathogens through unique antigens.
• Immune cells' receptors distinguish pathogens via unique antigens.
• It recognizes an unlimited number of antigens, mounting specific defenses.
• Activation of cells is required, which can take weeks.
• It exhibits memory, leading to stronger responses upon subsequent exposures.

White Blood Cells

• Include myeloid cells, lymphocytes, and natural killer cells.
• Myeloid cells are part of the innate immune response.
• Basophils, eosinophils, neutrophils, and macrophages (monocytes) are myeloid cells.

Phagocytic Cells

• Bind to and internalize pathogens in a phagosome.
• It then merges with lysosomes to destroy pathogens.
• Neutrophils, macrophages, and dendritic cells are phagocytic.
• These cells release cytokines.

Neutrophils

• Primarily ingest and destroy pathogens, a process called phagocytosis.
• Phagocytosis occurs when a pathogen is put in a phagosome.
• Two methods of destruction are employed: granules and oxidative burst.
• Granules fuse with the phagosome to form the phagolysosome, lowering the pH to kill 2% of pathogens.
• The oxidative burst involves producing reactive oxygen species, destroying proteins and nucleic acids.

Dendritic Cells

• Derived from monocytes, they ingest pathogens and present antigens to T cells.
• They function as antigen-presenting cells and are found where external antigens are encountered.
• Dendritic cells phagocytose pathogens, break their proteins into antigens, and present these to T cells in lymph nodes.
• Dendritic cells are the only cells that travel from skin/GI mucosa to lymph nodes (where T cells circulate).

Antigen-Presenting Cells

• T cells can only recognize antigens when presented on a Major Histocompatibility Complex (MHC).
• Antigen-presenting cells load antigens onto MHC molecules for T cell recognition.

Lymphocytes

• Includes B cells, T cells, and natural killer cells.
• B and T cells are part of the adaptive immune response.
• Natural killer cells are part of the innate immune response.
• B cells and natural killer cells mature in the bone marrow.
• T cells mature in the thymus.

Natural Killer Cells

• Target cells infected with intracellular organisms (viruses) and cancer cells.
• They kill target cells by releasing cytotoxic granules that punch holes in the cell membrane or by releasing molecules that cause apoptosis.

B Cells

• B cells convert to plasma cells to make antibodies.
• This occurs by finding an antigen and presenting it to a T cell, which then triggers the B cell's transformation into a plasma cell.
• B cells are also considered "antigen-presenting cells".
• They are specific, with receptors binding only to matching antigens.
• B cells bind antigens directly, without needing presentation on MHC molecules.
• Process:
  • A B cell binds to an antigen on a pathogen's surface, internalizes and degrades it, loads it onto an MHC molecule, and presents it to a T cell.
  • The T cell is activated by the antigen, triggering the B cell to mature into a plasma cell.
  • The plasma cell then secretes antibodies against that specific pathogen.
• Antibodies have the same antigen specificity as the B cell they originate from.
• Antibodies circulate in the blood and attach to pathogens, "tagging" them for destruction.
• This tagging action is specific to the pathogen that the B cell initially bound to.
• Antibodies are essentially the B cell receptor.
• Humoral immunity: antibodies float freely in the blood.

T Cells

• T cells exist in two types: helper cells, which aid other immune cells, and cytotoxic cells, which kill pathogens.
• T cells only start to work and mature when antigen-presenting cells present antigens to them.
• They are antigen-specific.
• Naive T cells mature by attaching to antigen-presenting cells, usually dendritic cells.
• Two main types: CD4 and CD8.

CD4 = helper cells

• Only recognize antigens presented on the MHC II molecule
• They secrete cytokines to coordinate the actions of other immune cells.

CD8 = cytotoxic T cells

• ONLY RECOGNIZE ANTIGENS PRESENTED ON MHC I MOLECULES
• They kill target cells.
• Only kill cells that carry the specific antigen that they match.

Innate Immune Response Actions

• Bacteria encounters a macrophage, which ingests the bacteria and releases cytokines.
• Released cytokines make blood vessels leaky and attract eosinophils, basophils, and mast cells.
• Neutrophils from the blood arrive and phagocytize the pathogens, often being destroyed in the process.
• Immature dendritic cells digest pathogens in tissues and travel to the lymph node.
• In the lymph node, dendritic cells present the antigen on an MHC II protein to a naive T cell.
• This is the first connection between the innate and adaptive immune systems.

Adaptive Immune Response Action

• Bacteria can directly enter lymph nodes and encounter B cells.
• Specific B cells phagocytose the bacteria and present it to naive CD4+ T cells.
• Viruses live in the cytoplasm of host cells, which then express the viral antigen on an MHC I molecule.
• Cytotoxic T cells recognize the antigen on the MHC I molecule, attach, and kill the infected cell.
• After the T cell interacts with its specific antigen, it undergoes differentiation and clonal expansion.
• CD4+ T cells then make the presenting B cells transform into plasma cells, which secrete antibodies.

MHC Molecules

• T cells can only bind to antigens that are displayed on a Major Histocompatibility Complex Molecules (MHC Molecules).
• Also called human leukocyte antigens (HLA).
• Found on the surface of cells.

MHC class I molecules

• Found on all nucleated cells in the body (except RBCs).

MHC class II molecules

• Only found on antigen presenting cells (macrophages, dendritic cells, and B cells).
• Ensure that T cells recognize and react to antigens.

MHC Class I Molecules

Structure

• alpha chain
  • Three domains: alpha 1, alpha 2, and alpha 3
  • Peptide binding groove
    • = Alpha 1 + alpha 2
    • Binds the antigens = peptides about 8-10 amino acids long
    • Have hydrophobic residues that bind to the hydrophilic amino acids inside the peptide binding groove
  • Transmembrane region
    • Anchors the MHC class I molecule onto the cell surface
• beta-2-microglobulin chain
  • Linked to the alpha chain
  • Binds between the 3 domains = props the whole structure

Action

• Peptide is displayed on the outside of the cells
• Cytotoxic T cells and Natural Killer cells attach to the antigen in the MHC I molecule
• If the cells (T cell or NK Cell) recognize the antigen → cell is attacked

MHC Class II Molecules

• Found only in antigen-presenting cells.
• These cells ingest an organism and put the antigen into the MHC Molecule.
• Only present to T-helper cells (also referred to as CD4+ cells)

Structure

• 2 chains
  • Alpha chain
    • Alpha 1 domain
  • Beta chain
    • Beta 1 domain
  • Both chains penetrate the cell membrane
• Groove that binds antigen (peptide chain)
  • Binds larger peptides: 14-20 amino acids

T Cells - General

• Express two groups of molecules on their cell surface to determine which type of T-cell they are: Helper T-cells or Cytotoxic T-cells.
• Express the CD3 Complex for binding to the antigen and the MHC Molecule itself.
• Express either CD4 or CD8, which also bind to the MHC Molecule to secure the interaction.
• T-cells start out naive and then get “activated”, resulting in a “differentiation” into effector T cells.
• Cytokines present around the cell determine the type of T cell it will become.

Helper T cells

• Express CD4 on their surface.
• The main function is to support other immune cells.
• Respond to MHC Class II molecules.
  • Present on antigen-presenting cells only.

Cytotoxic T cells

• Express CD8 on their surface.
• The main function is to kill infected cells.
• Respond to MHC Class I molecules.
  • Present on all nucleated cells in the body.

CD3 Complex

• Complex on the T Cell membrane that binds the antigen and the MHC Molecule.
• 2 Binding sites:
  • Antigen Binding Site
    • Alpha chain + beta chain
    • Each has two domains: variable domain and a constant domain
      • Constant Domain
        • Transmembrane segment
          • Cysteine residues = disulfide bond → chains connect to each other
        • Cytoplasmic segment
      • Variable Domain
        • Of alpha and beta regions
        • Combine to form the antigen-binding site
    • There is only 1 antigen binding site
  • MHC Binding Site
    • Part of the CD3 complex that does NOT bind to the antigen (rest of the CD3 Complex).

CD4/CD8 Molecules

• Sit next to the CD3 Complex.
• Bind to the MHC Molecules = secures the interaction between the T cell receptor and the MHC molecule.
  • CD4 = binds to MHC Class II
  • CD8 = binds to MHC Class I

Activation of T Cells

• Activation occurs when a T-cell encounters its pathogen's antigen in an MHC Molecule.
• Requires 2 Signals:
  • T Cell Receptor binds the antigen (on the MHC complex).
    • Signal goes down the CD3 Complex AND CD4 or CD8 molecule
  • Co-Stimulation
    • Ligand CD 28 on the T cell binds with B7 molecule on the antigen-presenting cell

CD28 (For Co-Stimulation)

• Structure on the surface of the T cell that binds to B7, a structure on the antigen-presenting cell.
• Antigen presenting cells start expressing higher levels of B7 on their surface when there are inflammatory cytokines around (interferon-gamma, IL-1 beta, and TNF-alpha).
• This binding is the second step required to activate the T cell.
• If a T cell binds to an antigen but this second step does not happen, the T cell will NOT activate = Anergy

Immune Synapse

• T cell receptor is bound to antigen + CD4/CD8 bound to MHC + B7 is bound to CD 28

Helper T-Cell Clonal Expansion

IL-2 and the IL-2 Receptor

• IL-2 is a cytokine.
• Activated T-helper cell starts making IL-2 and upregulates its IL-2 receptor.
• The activated T cell upregulates the alpha component of the IL-2 receptor → increases the affinity of the receptor for IL-2
• The IL-2 receptor has three protein components - alpha, beta, and gamma.
• Naive T cell only expresses the beta and gamma components. Have low affinity for IL-2.
• Alpha component has a high affinity for IL-2

IL-2 Production

• Activated T helper cell begins making lots of IL-2.
• Active T cells bind to IL-2 that they make (autocrine stimulation) → Activated T-helper cell starts to rapidly undergo cell division (clonal expansion).

T-Helper Cells

General

• Categories of T-helper cells.
  • T-helper type 1 (Th1)
  • T-helper type 2 (Th2)
  • T-helper type 17 (Th17)
  • T follicular helper cells (Tfh)
  • T regulatory (Tregs)

Cytokines

• Originate from antigen-presenting cells.
  • Depend on the type of pathogen present - help tailor the immune response to the specific pathogen

Cell Types of T-Helper Cells

• When these cells are activated, the cytokines trigger genetic changes (via transcription factors.)
• The specific helper T-cell will then secrete its own cytokines to help it perform its functions!

Th1 Cells

• Increase the ability of macrophages to kill organisms and increases proliferation of NK cells, Cytotoxic T-cells, and B cells.
• Cytokines bind to T cell receptor → cause it to make transcription factors that cause the T cell to transform to a Th1 cell.
  • Cytokines come from the following:
    • Macrophages and dendritic cells infected with viruses and intracellular bacteria.
    • Natural killer cells.
    • Cells infected with viruses.
• A Th1 cell then secretes interferon-gamma.
  • Boosts macrophages’ ability to kill ingested pathogens via the oxidative burst.
    • Increasing production of reactive oxygen species: Nitric oxide, Lysosomal proteases.
• Th1 cells express CD40 ligand on their cell surface.
  • Binds to the CD40 receptor on macrophages → stimulates them.
• Th1 cells produce IL-2.
  • Makes natural killer cells, CD8+ T cells, and B cells proliferate.

Th2 Cells

• Increase production of IgE by B-cells, coating worms and stimulating cells to release granules, while also recruiting eosinophils.
• Fight parasitic infections.
• Macrophages and dendritic cells exposed to parasitic worm secrete cytokines that bind to T cell receptor → cause it to make transcription factors that cause the T cell to transform to a Th2 cell.
• Th2 cell produces cytokines that stimulate B cells to make IgE
• IgE coats parasitic worms.
• IL-5 recruits eosinophils to the site of infection → they accumulate and degranulate → kill the parasite
• Th2 cells stimulate mast cells and basophils to bind to the Fc region of IgE.
• This triggers those cells to degranulate → kills the parasite

Th17 Cells

• The cytokine made by the Th17 cells recruits neutrophils!
• Fight bacterial and fungal infections.
• Dendritic cells and macrophages that have interacted with extracellular bacteria and fungi stimulate T cell to become a Th17 cellRecognize bacterial pepitdoglycans, lipopeptides and fungal glycans.
• Th17 cell produces IL-17 → recruit neutrophils (engulf extracellular pathogens and destroy them)

T Follicular Helper Cells

• Help establish memory cells and plasma cells that make IgG.
• Live in the follicles of lymph nodes.
• Antigen-presenting cells produce cytokines that stimulate a T cell to become a Tfh cell.
• T -follicular helper cells then stimulate a B cell to transform into a Plasma cell that produces IgG (Memory Cell). -Tfh cell expresses CD40 ligand on its cell surface that binds to CD40 receptor on B cells → makes them express cytokine receptors
• Tfh cells produce IL-21 and interferon-gamma → stimulate B cells to differentiate into:
  • Memory cells
  • Plasma cells
  • Make IgG antibody

Cytotoxic CD8 Cells

• Cytotoxic T cells find potential targets by going cell-to-cell binding non-specifically.
• They use adhesion molecules like LFA-1 on their surface to bind to molecules like ICAM which is found on the surface of most cells.
• After loosely binding in this way, it tries to bind to that cell’s MHC I molecule.
• If the cytotoxic T cell cannot bind because the correct antigen isn’t present, then the cytotoxic T cell disengages and moves on to the next cell.
• On the other hand, if the cytotoxic T cell does bind strongly to the antigen, then the two cells engage with each other more strongly.

Attachement

Cytotoxic T cell recognizes its antigen in the MHC I molecule

• Binds to the infected cell via an “adhesion molecule” (called LFA-1) that binds to a molecule found on the surface of most cells in the body called “ICAM”
• Binds to the antigen in the cell’s MHC I molecule → LFA-1 molecule changes its confirmation to bind ICAM more tightly (“death embrance”)
• Cytoskeleton rearranges and forms the supramolecular activation cluster (SMAC) on its surface

Killing

• Cytotoxic T cell releases its granules; contain perforin and granzymes.
• Perforin punches holes in the lipid bilayer of the target cell.
• Granzymes trigger apoptosis in the target cell.
• Cytotoxic T cell disengages and moves on to another potential target cell.

Natural Killer Cells

• Kill target cells based on the number or strength of activating versus inhibiting signals they receive.
• Deliver granzymes and perforin (like cytotoxic T cells).
• Are part of the innate immune response and don’t respond to antigens.
• Recognize cell surface molecules on cells infected with viruses, intracellular bacteria, or cancerous cells.
• Recognize MHC class I molecules that are part of our body and do not kill it.
• If the MHC I molecule is absent or foreign → will kill the target cell.
• Many viruses try to hide from our immune responses by making their host cell remove MHC class I molecules → the cell then does not have the body’s MHC Molecules → NK cell kills it.

Antibody-dependent cell mediated cytotoxicity (ADCC)

• A cell infected with viral proteins is bound by IgG antibodies.
• NK cell surface molecule CD16 binds to the Fc portion of the antibody.
• Activating signal to the NK cells → it destroys the infected cell.
• Natural killer cells also produce cytokines to activate macrophages

Structure of the B Cell Receptor

General

• The receptor is essentially an antibody.
• Has two heavy chains and two light chains.

Fragment-antigen binding region (Fab region)

• Part of the B cell receptor that binds the antigen.
• Is the point where ends of the heavy and light chains meet.
• There are two Fab fragments on each B cell receptor.

Constant region/Constant fragment region (Fc)

• Remainder of the heavy chain.
• Each B cell receptor has two identical heavy and light chains = two identical antigen-binding sites.
• Chains are linked via disulfide bonds.
  • The two heavy chains are linked to each other.
  • Each heavy chain is linked to a light chain.
• Once a B cell will develops into a plasma cell, the receptor gets secreted as an antibody with exact same antigen specificity.

Heavy Chains and Immunoglobulin Isotypes

• Heavy chain changes as the B cell develops!
• 5 major types of heavy chains.
• Classes (isotypes) of immunoglobulins: IgM, IgD, IgG, IgA, and IgE.
  • The five types of immunoglobulins are encoded by heavy chain genes: mu, delta, gamma, alpha, and epsilon
• Early/young B cell: all receptors are IgM.
  • Expresses the mu heavy chain.
• As the B-cell matures, it will express IgD in addition to IgM → this B-cell is now considered a mature B-cell.
  • A mature B-cell can travel in the lymphatic system.
  • But, the B-cell is still considered naïve: has not been exposed to an antigen yet
  • Alternative splicing: process by which the cell expresses the heavy chain exons for both mu and delta

Lymph Node Structure and Function

• Scattered throughout the body.
• Millions of B cells, T cells, antigens, and antigen-presenting cells pass through these lymph nodes.

Entering the Lymph Node

• From lymphatics.
  • Through afferent lymphatic vessel.
• From blood: through the high endothelial venules (HEVs).
  • Special endothelial cells located at postcapillary sites of lymphoid organs.
  • Express adhesion molecules.
  • When lymphocytes pass through the HEVs they can bind to and move through the endothelial cells and slip right into the lymph node

Paracortical Region

• First portion where cells enter
• The T cells remain here

Cortical Region

• B cells migrate to the cortical region of the lymph node..
  • Form the primary lymphoid follicles.
• If a B cell gets activated → replicates in the follicle → forms a germinal center.
• Follicle with a germinal center = secondary lymphoid follicle.
• Antigens enter the lymph node through the afferent lymphatic vessel → travel to the follicle.
• Antigens interact with B cells in the follicle! .

B cell Activation

• Interaction with a pathogen (binds to the pathogen’s antigen) -Interaction with a complement fragment

B cell Activation by the Pathogen

• B cells recognize antigens and become activated by them .
  • B cells recognize wide variety of antigens: peptides, carbohydrates, and lipids
  • Don’t require antigen-presenting cells to present an antigen
  • Antigen crosslinks two+ B cell receptors → B cell is activated

B cell Activation by the Complement System

• Uses the receptor molecule CD21.
• C3d (from the complement system) binds to an antigen.
• The C3d-antigen complex then binds to CD21 on the B cell.
• B cell receptor is bound to an antigen AND has a CD21 that’s bound to an antigen → initiate B cell activation.

ACTIVATED B CELL

• Differentiates into a plasma cell to secrete antibodies.
• There are 5 different types of antibodies.
• B Cells need CD4+ T cells to start making antibodies (other than IgM):
  • An activated B cell can become a plasma cell and make the IgM antibodies
  • But, to make IgG, IgA, and IgE antibodies, the B cell needs to interact with a helper T cell (CD4+ cell).
• Process called Isotype switching — change in the DNA.
• Once the B cell switches its isotype it cannot go back to making IgM again!
• How it works:
  • B cell presents antigen (on an MHC class II molecule) to a CD4+ T cell.
  • T cell expresses molecule CD40L on its cell surface → binds to CD40 on the B cell surface.
  • Makes the B cell express cytokine receptors.
  • T cell secretes cytokines, which instruct the B cell on the type of antibody to start producing.
    • T cell secretes IL-4 and IL-5, B cell will become an IgE secreting plasma cell.
    • T cell secretes IFN-gamma, B cell will become an IgG secreting a plasma cell

Immunoglobulins (Antibodies)

• Made by plasma cells following B cell activation
• Attach to the antigen of one pathogen and one pathogen only.
• Also the B-cell receptor.

Major Classes of Immunoglobulins

• IgM, IgD, IgG, IgA, and IgE. Each has a different function, shape, and valence.

Immunoglobulin M (IgM)

• First antibody produced in all immune responses.
• Makes up 4% of all of the antibodies found in the serum.
• The B cell receptor.
• Has 2 different conformations.
  • Serving as B cell receptor: binds 2 antigens —“has a valence of 2”
• Secreted as an antibody: It joins up with 4 other antibodies (IgM types) and forms a “pentamer” structure, held together by a structure called the J chain — This pentamer structure can attach 10 antigens. Can be made without T cell help and does not rely on being exposed to an antigen first. Can work against carbohydrates and lipid antigens.
• The most effective antibody at activating the "complement pathway"*

Immunoglobulin G (IgG)

• The most abundant immunoglobulin: 75% of immunoglobulin found in serum.
• Can bind to 2 antigens.
• Function #1: serves as an opsonin — Part of the Opsonization Process: pathogens are coated with antibodies, makes it easier for phagocytes to pick them up and eat them.
• Function #2: activates the complement pathway — Specifically, the “classical” pathway which helps destroy extracellular pathogens, namely bacteria. Function #3: work with NK cells to perform “antibody dependent cell mediated cytotoxicity” kills cells infected with viruses, IgG binds to antigens on a viruses’ surface NK cell uses its CD-16 receptor to bind to the antibodies when two CD-16 molecules have bound to an antibody, which, in turn, is attached to the virus, the NK cell releases granzymes and perforin to kill the target cell.
• Function #4: Only antibody that can cross the placenta, protecting newborns from bacteria and viruses for 6 months.

Immunoglobulin A (IgA)

• 20% of the serum immunoglobulin.
• In the bloodstream, IgA exists as one structure that can bind 2 antigens (is a monomer).
• The primary antibody in “mucosal” sites, which are structures in the body that are lined with a mucosal membrane such as saliva, tears, breastmilk, and semen.
• In mucosal sites, plasma cells produce IgA antibodies as “dimers, and is Bound together by a J chian which can bind to 4 antigens (Valence of 4). Function: opsonin
• Binds to and neutralizes pathogens where they enter the body. Helps the body more easily get pathogens out of the body or destroy pathogens before they can enter the body, as those swept away by cilia in the mucosal tract, excreted out the GI and GU tracts, or degraded in the stomach or mouth by enzymes.
• Babies receive lots of IgA in breast milk which neutralizes pathogens in the GI tract

Immunoglobulin E (IgE)

• Monomer = valence of 2.
• Makes up only about 0.004% of the total serum immunoglobulin.
• Mount allergic and anti-parasitic responses where it binds to IgE receptors on mast cells, basophils, and eosinophils → triggers granule release from those cells to destroy large and complex pathogens such as worms and parasites.
• IgE gets made inappropriately to non-pathogenic targets such as Peanuts or tree pollen, where it Binds to Fc epsilon receptors on the mast cells which triggers degranulation and histamine release leading to mucus production, increased vascular permeability and swelling along with contraction of smooth muscle to result in wheezing.
• IgE plays roles in atopic dermatitis, seasonal allergies, and asthma.

Immunoglobulin D (IgD)

• < 1% of the serum immunoglobulin.
• Monomer; valence of 2.
• Found alongside IgM antibodies on mature B lymphocytes.
• Signals that new B-cells are ready to leave the bone marrow and enter circulation.

Innate Immune Response - Key features

• Cells are non-specific.
  • Don’t distinguish one invader from another invader.
• Response is fast, minutes to hours.
• No memory.
• Components:.
  • Barriers: Chemical and physical.
    • Lysozymes in tears.
    • Low pH in the stomach.
    • Epithelium in the skin and gut.
    • Cilia that line the airways.
  • Macrophages.

Macrophages

• Are the front-line of the immune system, residing in tissues meaning that they Encounter most pathogens before any of the other cells of the immune system!
• Recognize pathogens within minutes and eat pathogens.
• Distinguishes healthy host cells from pathogens (self versus non-self).

Pathogen associated molecular patterns PAMPs.

• These are the types of molecules on the surface of pathogens that the macrophages recognize and the attack!

Pathogen Associated Molecular Patterns - PAMPs

• Molecules that humans don’t have Types of PAMPs.
  • Bacterial wall components:
    • Peptidoglycan.
    • Lipopolysaccharide (LPS).
    • Lipoteichoic acid
  • Fungal wall components.
    • Mannan.
  • Flagella proteins (Bacteria and some parasites). Viral RNA or DNA

Macrophage actions:

• Swallows bacteria > Traps it in a phagosome.
• Phagosome fuses with lysosomes forms phagolysosome.
• Phagolysosome contains 2 types of granules: specific granules and azurophilic granules
  • Specific Granules: Act first, Contain proteases and hydrolases that are active at a neutral pH while potassium and hydrogen ions are drawn into the phagolysosome decreasing the pH and allowing the enzymes in the azurophilic granules to go to work
  • Azurophilic Granules: - Contains hydrolases and oxidative enzymes -Oxidative enzymes catalyze oxidative reactions that produce the oxidative burst. - Oxidative burst happens in macrophages and neutrophils produce nitric oxide (NO) and reactive oxygen species superoxide anion and hydrogen peroxide.

Complement System

• The result is the creation of a structure called the Membrane Attack Complex (MAC), that Creates a hole in the cell wall of a bacteria and destroys the bacteria via several pathways that trigger its Production.

Classical Pathway

• Triggered by An antibody that is bound to an antigen on the surface of the bacteria!

Lectin Binding Pathway

• Started by a protein (called Lectin) that binds to mannose, which is found on the outside of bacterial cell walls!
  • After this protein binds, a chemical reaction happens that then starts …. The Classical Pathway, which makes the MAC.

Alternative Complement Pathway

• Started by one of the complement proteins binding directly to the outside of the bacteria. — Triggers the OG Classical Pathway = Another way to make C3 Convertase

Classical pathway

• Comprises proteins C1 through C9: Each protein is inactive and becomes activated when it’s “cleaved”
  • C1 starts the process by binding to 2 antibodies that are bound to antigens on the bacterial cell wall with it being Divided into 3 components with the C1q component binding to the antibody and the C1r and C1s components are enzymes that will eventually activate C1!
• C1 consists of C1q subunits that bind to Fc portions of antibody-antigen complexes where- Each C1q can bind to 1 antibody-antigen complex so Each C1 molecule can bind 6 antibodies with C1r and C1s being serine proteases (enzymes that are hidden so they cannot perform their enzymatic activity). that change when 2 C1q portions bind to the Fc receptors of 2+ antibodies (that are bound to antigen), and, as a result, the conformation of the C1. Thus molecule exposes C1s and C1r serine protease sites for C1r to cleaves C1s to activate the complex.

The activated C1

• Cleaves C4 into C4a and C4b where C4a floats away while C4b binds to the surface of the pathogen, and the C1 also Cleaves C2 into C2a and C2b for C2a to Floats away resulting in C2b to join C4b on the surface of the pathogen to form to C3 convertase (C4b2b)

C3 Convertase

• Converts that structure into C5 Convertase by Cleaving C3 into C3a and C3b as C3b proteins bind close to the C3 convertase -> C5 convertase (C4b2b3b protein complex where a Single C1 can generate maybe 10 C3 convertases but a single C3 convertase can cleave over a 100. C3 proteins per second while staying Active for About 2 minutes which should Generate A lot of C3b very quickly where the C5 Convertase Cleaves C5 into C5a and C5b. with the Created Factors binding To 3 Other Proteins to Creat STRUCTURE THAT PENETRATES THE CELL MEMBRANE!
• C5b Binds to C6, C7, and C8 to result in the C5b-C6-C7-C8 Structure penetrating the pathogen’s cell membrane!
• C9 Is used to form a channel straight through the pathogen’s membrane to create the to the Membrane attack Complex is formed -> Creates a hole in a bacterial cell membrane

Lectin Binding Pathway

• Lectin protein binds to mannose on the bacterial cell membrane and Cleaves C4 and C2 to produce The C3 convertase and Proceeds same as classical pathway!

Alternative complement pathway

• As- C3b Binds to bacterial surface, which Binds Factor B to C3b on the bacterial surface which facilitates Factor D to cleave Factor B -> Ba and Bb Resulting in Ba Floats off to allow Bb is attached to C3b and thus creates C3 convertase, Which in Turns proceeds the pathway as inThe Classical Pathway to create the MAC with added features of Some Complement Proteins having Other Jobs to Perform in the Immune system!!!
• C3b and C5a + C3a= Opsonins.
  • Chemotaxins that recruit neutrophils, eosinophils, monocytes, and macrophages to the site of inflammation.
    • Anaphylatoxins – help basophils and mast cells degranulate, releasing in proinflammatory molecules histamine and heparin that Contraction of the smooth muscle causing Bronchial constriction with an Increased vascular permeability.
• The following factors Remove antigen-antibody complexes in the sequence = C1, C2, C3, and C4

Lymphatic System

• Functions:
  • Protects the body from invaders.
  • Maintains the fluid level in the body.
  • Absorbs dietary fat from the intestine.
• Composition:
  • Lymph
  • Lymphocytes (T cells and B cells)
  • Lymphatic vessels and plexuses
  • Lymph nodes
  • Lymphoid organs:
    • Organs that produce lymphocytes: Thymus and Bone marrow.
    • Organs that house lymphocytes: Lymph nodes Spleen Tonsils.

Lymph

• Clear-slightly yellow fluid transported through lymphatic vessels
• Origin of lymph is the fluid in the extracellular space as Lymphatic capillaries form lymphatic plexuses where Fluid enters the lymphatic capillaries

Lymphatic capillaries merge

• Lymphatic vessels drain lymph through lymph nodes eventually forming lymphatic trunks.
• The Lymphatic trunks converge to form two lymphatic ducts: right lymphatic duct and the thoracic duct.
• Collections:
  • Right lymphatic duct: from the right head, neck, and chest and the Right upper limb.
  • Thoracic duct from the Rest of the body: left head and neck, left chest, left upper limb, the abdomen and both lower limbs and Begins as cisterna chyli A dilated sac where the lymphatic trunks carrying lymph from the lower limbs, abdominal viscera, and the pelvis converge .
  • The thoracic duct travels through the thoracic cavity and eventually drains into the left venous angle for its lymph to -Get mixed with the blood! -Contents of the lymph from the right lymphatic duct and the thoracic duct drain into the superior vena cava to reach the right atrium of the heart! Right lymphatic drains into the right side veins. This is reversed too. . -Every day 20 liters of fluid leaves the capillaries and becomes part of the interstitial fluid between cells -About 17 liters gets quickly reabsorbed right back into the capillaries this -Leaves 3 liters of fluid behind in the tissues each day vessels collect excess interstitial fluid and return it to the blood -Once the interstitial fluid is in the lymphatic vessels, it’s called lymph Fluid and proteins make their way into the microscopic lymphatic all of the collected lymph is dumped into the veins

Lymphatic Capillaries

Are extremely permeable with walls made of endothelial cells that only loosely overlap, forming one-way mini-valves

These endothelial cells are anchored to structures in the interstitial space by collagen filaments, which allows the lymphatic capillaries to remain flexible but retain their overall shape

When the pressure in the interstitial space is greater than the pressure in the lymphatic capillary, the endothelial mini-valves open up, allowing fluid to enter.

• When the pressure in the interstitial space is less than the pressure in the lymphatic capillary, the endothelial mini-valves are pushed shut, keeping the lymph inside

Lymphoid Organs

• Lymphoid organs remove foreign material from the to keep it from entering the bloodstream, and act as lookout points for the body’s immune defenses

Diffuse lymphoid tissue

It’s a lLoose arrangement of lymphoid cells and protein, common in the lining of the gastrointestinal and respiratory tracts

Lymph nodes

• Are tightly packed balls of lymphoid cells and protein that cluster along the lymph vessels where Each is a few millimeters to about 1–2 cm in size
• Concentrated along the lymph trunks where they can be located along the neck, armpit, and groin, while in the intestinal wall one finds-Peyer’s patches
• Pathogens enter lymph nodes and encounter the immune system through Dendritic cells being able to continuously sample the lymph which present antigen to B cells and the resulting B cell turns into a plasma cells Producing antibodies which leave the lymph node to circulate throughout body.
• Circulating T cells move between the Nodes, lymph, and blood

Spleen

Sits on the left side of the body below the diaphragm and on top of the stomach and is split into The White and Red Pulp! -The white pulp has Antibody-coated bacteria are filtered out of circulation, where Antibodies are generated by B with The white pulp functioning like a giant lymph node that receives blood

Red Pulp

Defective

Explore the immune system's role in protecting against microorganisms, highlighting the innate and adaptive immune responses. Learn about the cells involved, including white blood cells, and their specific functions in defense.