Antigen

Substance that stimulates antibody formation and has the ability to bind to an antibody or to T lymphocyte antigen receptor but may not be able to trigger immune response

Antigen

The recognition of antigen by T cells and B cells is fundamentally different:

• B cells:

• T cells:

• B cells: recognize soluble antigen when it binds to their membrane-bound antibody

• T cells: recognize peptides (antigen) combined with MHC molecules on the surface of APC

The smallest part of an antigen that is seen by B cell receptors and T cell receptors

Epitopes

Epitopes are discrete regions of molecules called _

antigenic determinants

Different lymphocytes, each with different receptors, recognize different epitopes on the same antigen:

• B cells:

• T cells:

• B cell receptor: free-soluble molecules, surface bound molecules, degraded fragments of antigen

• T cell receptors: peptide-MHC molecule combinations presented on the surface of APC

3 Functional Categories of Antigens

• Haptens

• Immunogens

• Tolerogens

Functional Categories of Antigens

• Complete antigens

• Antigens that induce immune response either by producing antibody or sensitized lymphocytes which in turn react specifically with immunogens that produced them

Immunogens

Functional Categories of Antigens

• Partial antigens

• Small molecular weight substances that are antigenic, but incapable by themselves of inducing specific immune response

• Lack immunogenicity but can react with specific antibody when bound to an immunoge (carrier/larger molecule)

Haptens

Characteristics of Hapten

Functional Categories of Antigens

• Antigens which induce immune unresponsiveness in normal condition

• During development of immune repertoire, tolerance to self molecules and cells develop first.

• Therefore there is no immune response against the self-tissue in normal, healthy state

Tolerogens

3 Cellular Antigens of Immunologic Importance

• Major Histocompatibility Complex

• Autoantigens

• Blood Group Antigens

Cellular Antigens of Immunologic Importance

• Major Histocompatibility Complex (MHC)

→Found on _

→Also known as _

→Present peptide antigens to _

→Determines _

→Genes coding MHC molecules > _

→Found on NUCLEATED CELLS

→Also known as HUMAN LEUKOCYTE ANTIGEN (HLA)

→Present peptide antigens to T-CELLS

→Determines HISTOCOMPATIBILITY

→Genes coding MHC molecules > CHROMOSOME 6

Classes of MHC

HLA Allelles and their disease association

• HLA-B27

Ankylosing spondylitis

(a chronic inflammatory arthritis, primarily affecting the spine and sacroiliac joints, causing pain, stiffness (worse with rest, better with activity), fatigue, and potentially leading to spinal fusion (ankylosis), resulting in a hunched posture)

HLA Allelles and their disease association

• HLA-DR2

Good Pasteur Syndrome

(a rare autoimmune disorder where the immune system mistakenly attacks the body's own collagen in the lungs and kidneys, causing inflammation, bleeding (hemorrhage) in the lungs, and glomerulonephritis (kidney inflammation) leading to potential kidney failure and respiratory issues like coughing up blood and shortness of breath)

HLA Allelles and their disease association

• HLA-DR3

Systemic Lupus Erythematosus

(a chronic autoimmune disease where the immune system mistakenly attacks healthy tissues and organs, causing widespread inflammation affecting joints, skin, kidneys, brain, heart, and more)

HLA Allelles and their disease association

• HLA-DR4

Rheumatoid arthritis

(chronic autoimmune disease where the immune system mistakenly attacks the body's own tissues, primarily the synovium (joint lining), causing painful swelling, stiffness, and potential damage to cartilage, bone, and joints, often in the hands, wrists, and feet, symmetrically.)

HLA Allelles and their disease association

• HLA-DQ2, HLA-DQ8

Celiac disease

(autoimmune disorder where gluten (in wheat, barley, rye) triggers the immune system to attack the small intestine, damaging villi and preventing nutrient absorption, leading to digestive issues)

HLA Allelles and their disease association

• HLA-B51

Behcet's disease

(rare, chronic auto-inflammatory disorder causing systemic vasculitis—blood vessel inflammation—that leads to recurrent, painful mouth and genital ulcers, skin lesions, and eye inflammation)

HLA Allelles and their disease association

• HLA-B58

Myasthenia gravis

(chronic autoimmune disease causing fluctuating weakness in voluntary muscles, especially eyes, face, throat, arms, and legs, due to faulty nerve-to-muscle communication. It's caused by the immune system attacking acethycholine receptors, leading to fatigue with activity and improvement with rest_)

HLA Allelles and their disease association

• HLA-DR, HLA-DQ

• Type 1 DM

• Multiple sclerosis - a chronic autoimmune disease where the immune system attacks myelin, the protective sheath around nerves in the brain and spinal cord, disrupting nerve signals and causing varied neurological symptoms like vision problems, fatigue, numbness, weakness, balance issues, and cognitive changes.

Cellular Antigens of Immunologic Importance

• Autoantigens

→ Also called _

→The evolution of a recognition system that can recognize and destroy non-self material must also have safeguards to prevent damage to self antigens

→Failure to recognize self antigens can result is _

→ Also called SELF ANTIGENS

→The evolution of a recognition system that can recognize and destroy non-self material must also have safeguards to prevent damage to self antigens

→Failure to recognize self antigens can result is AUTOANTIBODIES

Cellular Antigens of Immunologic Importance

• Blood Group Antigens

→Widely distributed throughout the (3)

→A _ may result when foreign RBC antigens are introduced to a host

→Certain antigens (_) are structural components of the RBC membrane. If these are missing, RBC membrane is defective resulting in hemolytic anemia

→Widely distributed throughout the TISSUES, BLOOD CELLS, BODY FLUIDS

→A TRANSFUSION REACTION or HDN may result when foreign RBC antigens are introduced to a host

→Certain antigens (RH SYSTEM) are structural components of the RBC membrane. If these are missing, RBC membrane is defective resulting in hemolytic anemia

Chemical Nature of Antigens

Determinants of Immunogenecity (7)

• Molecular weight

• Chemical complexity

• Foreignness

• Antigenic determinants (Epitopes)

• Genetic constitution of the host

• Susceptibility to Tissue Enzymes

• Dosage, Route, and Timing of Antigen

Substance administered with an antigen or immunogen to increase the immune response

Adjuvants

Adjuvants

• Precipitates antigen to increase its _ and enhance antigen presentation and phagocytosis

• Stimulates _

• Activates macrophage and enhance phagocytosis and expression of co-stimulator such as _

• Used in _

• Precipitates antigen to increase its SIZE and enhance antigen presentation and phagocytosis

• Stimulates LOCAL INFLAMMATORY RESPONSE

• Activates macrophage and enhance phagocytosis and expression of co-stimulator such as MHC CLASS II

• Used in IMMUNIZATION

Antigen Receptors (2)

• The immune system depends upon receptors and the ligands bound by them for its function

• Preformed receptors - innate immune system

• Somatically generated receptors - adaptive immune system

Allow a quick response to confer some protection while adaptive immune system prepares to respond

Pre-formed receptors

6 Types of Pre-Formed Receptors

• Pattern Recognition Receptors

• Toll-like Receptors

• Killer Activation Receptors

• Killer Inhibition Receptors

• Complement Receptors

• Fc Receptors

Pre-Formed Receptors

• Recognize broad structural motifs (similarities in design) that are not present within the host and are generally found on microbes

Pattern Recognition Receptors

Pre-Formed Receptors

• Pattern Recognition Receptors

→Present in _

→Recognize _ which include combinations of sugars, proteins, lipids, and nucleic acids broadly associated microbes

→PRR binding to PAMPs trigger various forms of _ intended to destroy the pathogens

→Present in SOLUBLE FORMS or on HOST CELL SURFACES

→Recognize PAMPs which include combinations of sugars, proteins, lipids, and nucleic acids broadly associated microbes

→PRR binding to PAMPs trigger various forms of INFLAMMATION intended to destroy the pathogens

Pre-Formed Receptors

• Toll-like receptors

In humans, PRRs also include TLRs that are present on a variety of host cells

→ binding to TLR mediates the generation of defensive responses like _ ( to promote inflammation, attraction of macrophages, PMNs, NK cells, and dendritic cells to the site of infection)

• cytokine release

Pre-Formed Receptors

• Receptors found on NK cells capable of detecting alterations in host cells infected by pathogens (viruses)

Killer ACtivation Receptors

Pre-Formed Receptors

• Killer Activation Receptors

→Recognize presence of stress-related molecules (_ and _) expressed by host cells that are unhealthy or abnormal for various reasons

→Binding of _ or _ to KAR induces the NK cells to attach and destroy the targeted host cells

→Recognize presence of stress-related molecules (MICA & MICB) expressed by host cells that are unhealthy or abnormal for various reasons

→Binding of MICA or MICB to KAR induces the NK cells to attach and destroy the targeted host cells

Pre-Formed Receptors

• Receptors used by NK cells to monitor MHC class I molecules normally displayed on cell surfaces of all nucleated cells in the body

Killer Inhibition Receptors

Pre-Formed Receptors

• Killer Inhibition Receptors

→Many processes, including cancers or viral infections, decrease the number of _ molecules displayed on the surface of affected cells

→Once bound to target cells via KARs, NK cells use KIRs to assess MHC class I expression on that cell

MHC class I

Pre-Formed Receptors

• Certain complement components or fragments bind to microbial surfaces and tag microbes for destruction by other elements of the immune system

Complement Receptors

Pre-Formed Receptors

• Complement Receptors

→Cell surface-bound complement receptors on phagocytic cells and B cells recognize these bound complement fragments and facilitate binding, ingestion, and internal degradation of tagged microbes

---------------------------

Pre-Formed Receptors

• Expressed on the surface of phagocytic cells to recognize and bind epitope-engaged antibodies

Fc Receptors

Pre-Formed Receptors

• Fc receptors

→Epitope binding by (3) triggers a conformational change in the _ portion of the antibody

→Binding results to _ of epitope-antibody-FcR complex

→Epitope binding by IgA, IgG, or IgM triggers a conformational change in the TAIL or Fc portion of the antibody

→Binding results to PHAGOCYTOSIS of epitope-antibody-FcR complex

Specialized receptors of the adaptive immune system that are regenerated anew in the lymphocytes of every individual through somatic chromosomal rearrangements and mutations

Somatically Generated Receptors

Somatically Generated Receptors (2)

• B cell Receptors (BCR)

• T cell Receptors (TCR)

Somatically Generated Receptors

• Composed of monomeric IgG ssociated with disulfide-linked heterodimers Igα and Igβ

B Cell Receptors

Somatically Generated Receptors

• B Cell Receptors

→When a BCR binds to an epitope, the specialized cytoplasmic tails of _ initiate an intracellular signalling cascade that may lead to B cell activation

→Some activated B cells, terminally differentiate into _ which secrete Igs

• Igα and Igβ

• plasma cells

Somatically Generated Receptors

• Structurally similar to Igs

• Heterodimers with an αβ or γδ chain pair

T Cell Receptors

Somatically Generated Receptors

• T Cell Receptors

→Membrane bound receptors and recognize antigen combined with _

→Associated with _ which links TCR with intracellular signalling molecules

→_ or _, an accessory molecule, acts as co-receptor for TCR

• MHC molecules

• CD3

• CD4 or CD8

T Cell receptor