Lecture 3 Objectives

Antigen (Ag)

Any molecule that can specifically bind to an antibody or a T cell receptor. Not all antigens stimulate a full immune response.

Immunogen

An antigen that does trigger an adaptive immune response on its own.

• All immunogens are antigens, but not all antigens are immunogens.

Epitope

The specific region of an antigen that is recognized by antibodies or T cells.

• B cells/antibodies bind external epitopes (linear or conformational).

• T cells recognize internal peptide fragments presented by MHC.

Hapten

A small molecule that is antigenic but not immunogenic by itself. Needs to bind to a carrier protein to trigger a response

Host Factors Influencing Antigen Response

• Age:

  • Neonates → weak, immature responses (maternal antibodies help).

  • Elderly → immune function declines.

• Health: Malnutrition, stress, fatigue, or underlying disease = weaker immunity.

• Genetics: Inherited differences in BCRs, TCRs, and MHC proteins determine which antigens each person can recognize.

Antigen Factors Influencing Response

• Dose:

  • Small dose → may be cleared by innate immunity.

  • Moderate dose → adaptive response.

  • Very high dose → tolerance (no response).

• Route of entry:

  • IV → goes to spleen.

  • Subcutaneous/intradermal → local lymph nodes.

  • Oral → mucosa-associated lymphoid tissue (MALT).

• Size: Larger molecules (>10 kDa, often >100 kDa) are more immunogenic.

• Foreignness: More different from self = stronger response.

• Composition/complexity:

  • Proteins → strongest (many structures).

  • Carbs → weaker.

  • Lipids/DNA → poor unless attached to carrier.

  • Repetitive synthetic molecules → usually no response.

• Processability: Must be broken down and presented on MHC to trigger T cells.

Autoantigens

Self-antigens. If immune system reacts → autoimmune disease

Alloantigens

Antigens from another individual of the same species (e.g., organ transplant)

Heteroantigens

Antigens from a different species (e.g., xenotransplant)

Heterophile antigens

Structurally similar antigens found in unrelated species. → Can cause cross-reactive antibody responses. Example: ABO blood group antigens share similarity with bacterial structures

Cytokines (definition and how they act)

Messenger proteins secreted by immune cells

• Paracrine (nearby cells), autocrine (same cell), endocrine (long-distance)

Cytokine functions

• Activate/inhibit gene transcription.

• Direct cell growth, survival, differentiation.

• Drive inflammation or anti-inflammation.

• Regulate adaptive immunity

Cytokine Traits

• Redundancy

• Pleiotropy

• Synergy

• Antagonism

Redundancy

different cytokines, same effect

Pleiotropy

one cytokine, many effects

Synergy

cytokines enhance each other

Antagonism

one cytokine blocks another

Cytokine Networks

Cytokines often act in cascades, creating feedback loops

Innate Cytokines

(early, nonspecific defense)

• Innate cytokines can activate adaptive immunity (e.g., IL-12 pushes T cells toward Th1; IL-6 helps Th17 differentiation).

• IL-1 (α, β)

• TNF-α

• IL-6

• TGF-β

• IFN-α/β

• Chemokines (e.g., IL-8)

IL-1 (α, β)

inflammation, fever, acute-phase proteins

TNF-α

inflammation, fever, ↑ vascular permeability; septic shock

IL-6

pro- and anti-inflammatory; stimulates B/T cells, acute-phase proteins

TGF-β

anti-inflammatory; inhibits T cells and macrophages

IFN-α/β

antiviral; activate NK cells; ↑ antigen presentation

Chemokines (e.g., IL-8)

recruit immune cells via chemotaxis

Adaptive Cytokines

helper T cell subsets

• Th1

• Th2

• Th17

• Treg (Regulation)

Th1

(cell-mediated immunity): IFN-γ, IL-2 → activate macrophages, NK cells, cytotoxic T cells

Th2

(humoral immunity): IL-4, IL-5, IL-13, IL-10 → stimulate B cells, antibodies, allergy, parasites

Th17

(extracellular defense): IL-17, IL-23 → recruit neutrophils, inflammation, mucosal defense. Dysregulation = autoimmune disease

Greg (Regulation)

IL-10, IL-35 → suppress immune responses, prevent autoimmunity

Chemokines

• Specialized cytokines that direct cell movement (chemotaxis).

• Recruit white blood cells to infection sites.

• Families: CXC, CC, C, CX3C (classified by cysteine motifs).

• Example: IL-8 (CXCL8) attracts neutrophils.

Hematopoietic Growth Factors

• Cytokines that regulate blood/immune cell production in bone marrow.

IL-7

lymphoid lineage (T & B cells).

IL-3

works with others for multiple cell types

GM-CSF 

granulocytes + macrophages.

M-CSF

monocytes/macrophages.

G-CSF

neutrophils

IL-5 (with IL-3, GM-CSF)

eosinophils

Erythropoietin

red blood cells (clinically treats anemia).