Lecture 9 Antibodies and Immune Responses

Ligand

A molecule that binds specifically to a protein.

Immune Response

Reaction to unrecognized substances in the body.
-distinguishes molecular "self" from "nonself" and destroys "nonself"
-Eliminated viruses, bacteria, and other pathogens and molecules
-Coordinated interactions among many classes of proteins, molecules, and cell types

Primary Immune Response

First exposure to an antigen.

Secondary Immune Response

Response after subsequent exposures to an antigen.

Humoral Immune System

directed at extracellular bacterial infections and viruses
-antibodies
-Memory B cells

Cellular Immune System

Destroys intracellular pathogens and cancers from infected host cells, parasites, and foreign tissues.
-Antigen presentation
-Cytotoxic T-cells
-Memory T cells

Antigen

Substance that elicits an immune response.
-could be a virus, a bacterial cell wall, an individual protein, or other molecule

antibodies

bind to an epitope (antigenic determinant) within the antigen
-interaction is strong and specific

Epitopes

Specific regions on antigens recognized by antibodies.

Haptens

Small molecules that elicit immune responses when covalently bound to large proteins.

Helper T Cells

A type of T lymphocyte that have CD4+ receptor on their surface
-Activated when their TCR binds to an antigen presented by an APC in combination with MHC class II molecules
-Do not directly kill infected cells
-"Help" by activating other immune cells via cytokines

Cytokines

small signaling proteins released by cells that regulate inflammation, immune responses, and intercellular communication

B cell activation

Key function of Th cells
-The B cell presents and antigen to t a helper T cell
-Th can recognize the antigen and secrete cytokines that trigger B cell differentiation into a plasma cell

Activation of Cytotoxic T cells

Key function of Th cells
-Helper T cells release cytokines that promote the differentiation and proliferation of cytotoxic T cells, which can then kill infected cells directly

Macrophage Activation

Key function of Th cells
-Macrophages present antigens to helper T cells, which then secrete cytokines to enhance the macrophages' ability to destroy pathogens

Regulation

Key function of Th cells
-Intensity and duration of immune responses
-The balance between humoral response and cellular responses

Th1 Cells

Promote cellular immune response by activating macrophages and cytotoxic T cells to eliminate intracellular pathogens (viruses and bacteria)

Th2 Cells

Promote humoral immune response, particularly in response to extracellular pathogens (like parasites)
-B cell activation and antibody production

Th17 Cells

Target extracellular bacteria and fungi, associated with inflammation.

T Regulatory Cells

Help regulate or suppress immune responses
-important for preventing autoimmune diseases by maintaining immune tolerance

Cytotoxic T Cells

(Tc cells or CD8+ cells) recognize and directly destroy infected or abnormal cells upon recognition of antigens bound to MHC class I molecules
-leads to the production of cytokines that stimulate the selective production of Tc cells that can bind to a particular antigen

Helper T eclls

(Th or CD4+ cells) recognize antigens presented on MHC class II molecules by antigen-presenting cells (i.e., macrophages or B cells)
-leads to production of cytokines that simulate the selective proliferation of B cells that can bind to a particular antigen

Major Histocompatibility Complex (MHC)

Molecules presenting antigens on cell surfaces.

Clonal Selection

Process of selecting specific immune cells for response.

Leukocytes

immune cells that protect against infections, foreign invaders, and diseases
-Circulate in the blood and can migrate into tissues

leukocyte functions

-Defend against infection by identifying, engulfing and destroying pathogens
-Initiate immune responses (recognize foreign antigens and activate a response)
-Remove dead or damaged cells (phagocytosis)
-Mediate inflammation and allergic reactions (release signaling molecules such as cytokines and histamine)

Granulocytes

Leukocytes with granules, including neutrophils, eosinophils, and basophils.

Neutrophils

-The most abundant WBC
-First responders to infections
-Phagocytose pathogens
type of granulocyte

Eosinophils

type of granulocyte that is primarily involved in parasitic infections and allergic reactions

Basophils

least common type of granulocyte
-release histamine during allergic responses
-Help mediate inflammation

Agranulocytes

Leukocytes without granules, including lymphocytes and monocytes.

Lymphocytes

B cells, T cells, and natural killer cells, which are crucial for adaptive immunity
-B cells produce antibodies, T cells are involved in cell-mediated immunity, and NK cells target virus-infected or cancerous cells

Monocytes

The largest type of leukocyte

-Circulate in the bloodstream and migrate into tissues where they differentiate into macrophages and dendritic cells

-Macrophages phagocytose pathogens and dead cells

-Dendritic cells are critical for antigen presentation to T cells

Antibody mediated immunity

-Antibody = immunoglobulin = (Ig)= quaternary proteins that bind bacteria, viruses, or large molecules identified as foreign and target them for destruction
-Produced by B lymphocytes or B cells

B Cells Activation

activated by an antigen and helper T cells

-Activated B cells turn into plasma cells that mass produce antibodies

Memory cells

permit a rapid response to pathogens previously encountered

Vaccines

-Often consist of weakened of killed virus or isolated proteins from a viral or bacterial protein coat
-Presents viral particle to the immune system, "teaching" it what the viral particles look like, thus stimulating the production of memory cells

Immunization

Process of building protection against diseases.

Evidence-Based Medicine

Practice of using research to inform clinical decisions.

Immunoglobulin Classes

Five antibody (Ig) classes identified by heavy chain type.

IgA

Antibody that protects against pathogens in mucosal linings (gut, lungs, urogenital tract), saliva, tears, and breast milk

IgD

-A B-cell surface receptor
-Has potential role in cell differentiation

IgE

-Triggers histamine release from mast cells and basophils

-Also protects against parasitic worms

-AllergiEs & and Asthma ...E

IgG

Primary antibody responsible for antibody-based immunity
-The only antibody able to cross the placenta and protect a fetus
-G for Gestation

IgM

-A B-cell surface receptor

-Can be a monomer or pentamer

-First line of defense before IgG can be produced in sufficient quantities

Immunoglobulin G (IgG)

One of the most abundant blood serum proteins
-4 polypeptide chains: 2 heavy and 2 light chains
-Cleavage with protease papain releases the basal fragment Fc and two Fab branches (each with a single antigen-binding site)
-Constant domains contain the immunoglobulin fold structural motif

Antigen-Binding Sites

Antibodies have two identical sites for binding.

Variable Domain of IgG

-Associate to create the antigen-binding site
-VDJ recombination allows for unique paratope generation
-Allows formation of an antigen-antibody complex

VDJ Recombination

Process generating diverse antibody binding sites.

Phagocytosis of Antibody-Bound viruses

When Fc receptors bind and antibody pathogen complex, macrophages engulf the complex

Induced fit

the antibody and/or antigen change structures to make a better fit
-Kd values as low as 10^-10 M

Polyclonal antibodies (pAbs)

-Inject an antigen into a subject

-Different B cells will recognize different epitopes of the same antigen

-Different antibodies will be made against the same antigen

-pAbs are heterogenous; recognize different epitopes

Monoclonal Antibodies (mAbs)

-Inject an antigen into a subject

-Isolate one B cell

-Culture that cell to create many clones

-mAbs are homogenous; all recognize the same epitope

Western Blot

Technique using antibodies to detect specific proteins.

Immunoaffinity

The chemical affinity between antibody and antigen

-The interaction is both strong and selective

-Useful for clinical and research purposes (ELISA (sandwich))

Autoimmune Disease

Immune system mistakenly attacks body's own tissues, organs, or cells.

-self-tolerance is disrupted for a variety of reasons, but commonly due to molecular mimicry

-Leads to the production of autoantibodies or the activation of autoreactive T cells that target a healthy body

Molecular Mimicry

specific form of molecular cross-reactivity

-antibodies bind normal tissues because a foreign antigen shares close structural similarity with a self-antigen

Rheumatoid Arthritis

Chronic inflammation targeting synovial joints.

Systemic Lupus Erythematosus

systemic autoimmune disease affecting multiple organ, including the skin, kidneys, heart, and brain
-AI target DNA, nuclear proteins, and other cellular components

Type 1 Diabetes

Immune attack on insulin-producing pancreatic beta cells.

Multiple Sclerosis

A disease of the central nervous system where the immune system attacks the protective myelin sheath covering nerve fibers.
Immune system attacks myelin in the CNS.

Hashimoto's Thyroiditis

An autoimmune disease where the immune system attacks the thyroid gland, leading to hypothyroidism
-AI target: Thyroid gland

Graves' Disease

an autoimmune disease where autoantibodies bind thyroid receptors and have the same effect as thyroid stimulating hormone. Causes hyperthyroidism, leading to symptoms like rapid heartbeat, weight loss, and anxiety.
-AI Target: Thyroid-stimulating hormone receptor

Celiac Disease

Immune reaction to gluten damaging the small intestine.
AI Target: Small intestine

Addison's Disease

The immune system attacks the adrenal glands, reducing their ability to produce hormones like cortisol
-AI Target: Adrenal glands

Inflammatory Bowel Disease

Includes Crohn's disease and ulcerative colitis, where the immune system attacks parts of the digestive tract
-AI Target: Gastrointestinal tract

Myasthenia Gravis

A neuromuscular disease that leads to muscle weakness, especially in the eyes, face, and throat.
-AI Target: Acetylcholine receptors at the neuromuscular junction

Ankylosing Spondylitis

A type of arthritis that primarily affects the spine, causing chronic inflammation and potentially leading to spinal fusion
-AI Target: Spine and sacroiliac joints

Sjogren's syndrome

An autoimmune disorder characterized by dry eyes and dry mouth due to the immune system attacking the glands that produce saliva and tears.
-AI Target: Salivary and lacrimal glands

Pernicious Anemia

A condition where the body cannot absorb vitamin B12 due to immune destruction of stomach cells that produce intrinsic factor, essential for B12 absorption
-AI Target: Parietal cells in the stomach

Vitiligo

A condition where the immune system attacks melanocytes, the cell responsible for producing pigment in the skin, leading to white patches.
-AI Target: Melanocytes

Scleroderma

An autoimmune disease that results in the hardening and tightening of the skin and connective tissues
-AI Target: Connective tissues and skin

Guillain-Barre Syndrome

A rare autoimmune disorder where the immune system attacks the peripheral nerves, leading to muscle weakness and paralysis
-AI Target: Peripheral nervous system

Lateral Flow Assays

Diagnostic tests using antibodies for analyte detection.
-Analyte is flowed over a solid phase with bound antibody
-Labeled secondary antibodies bind antigen

Inflammadry

-A lateral flow assay to detect for matric metalloproteinase-9 (MMP9)
-MMP9 is a general inflammatory and dry eye biomarker

Anti-VEGF Therapy

Monoclonal antibodies target and bind VEGF-A so it can't bind to VEGF-receptors

Ranibizumab

Antibody fragment targeting VEGF-A for eye treatment.

Bevacizumab (Avastin)

Full length antibody against VEGF-A. Originally used as a cancer treatment.

Aflibercept

Fusion protein trapping multiple angiogenic factors.
-Binds VEGF-A, VEGF-B, and placental growth factor
-A broader inhibitor of angiogenesis binding multiple angiogenic factors
-NOT AN ANTIBODY