2. How to Speak like an Immunologist

Lecture 3

Why does immunology feel overwhelming at first?

• Detail-heavy science

• Many abbreviations

• Molecule names sound similar

• Tests picky on small details

• Feels like “too much to memorize”

At the simplest level, what makes up immunity?

• System of cells and molecules

• Example cell: Macrophage (Kirby)

• Example molecule: Immunoglobulin (Antibody)

What are the two major arms of immunity?

• Innate immunity

  • Hard-wired, evolutionary conserved

  • Has humoral (molecules in fluid) and cellular (cells) components

• Adaptive immunity

  • Built for variability, more flexible

  • Also has humoral and cellular components

Who are the immune cells?

White blood cells (leukocytes)

Why are they called “white” blood cells?

• Centrifuged blood separates into layers:

  • 55% plasma (top)

  • <1% buffy coat (WBCs + platelets)

  • 45% erythrocytes (RBCs)

• WBCs sit in the pale “buffy coat”

Examples of immune cells (non-lymphocytes)?

• Macrophage

• Monocyte

• Neutrophil

• Eosinophil

• NK cel

Examples of lymphocytes (special group of WBCs)?

• CD8 T cell

• CD4 T cell

• Regulatory T cell

• B cell

Where do immune cell names often come from?

• Latin or Greek roots

• Example:

  • Leuko (Greek: white) + cyte (Greek: container/body) = “leukocyte”

  • Lympho (from lymphatic tissues or lymph nodes) + cyte = “lymphocyte”

Where do immune cells come from?

• Derived from stem cells in bone marrow

• Process: differentiation (stem cell → specialized cell type)

• Cell fate = the “end” type chosen (e.g., RBC fate vs. WBC fate)

What happens once immune cells are differentiated?

• Circulate in the blood

• Migrate (“home”) to different tissues and organs

• Adapt to local environments

• Scan for infection and perform homeostatic functions

  • Homeostatic: opposite of defense

How are immune cells different from organ-specific cells like liver or kidney cells?

• Liver/kidney cells: stay in their organ and serve one function

• Immune cells: travel through body, adapt to tissues, scan for invaders

What is a cell?

• Individual unit of an organism

• All cells (except RBCs) have a nucleus with DNA

If all cells have the same DNA, why are they different?

• Not all genes are expressed in every cell

• DNA → mRNA → Protein = gene expression

  • Transcription + translation = gene expression

• Different cells express different proteins

  • Macrophage: doesn’t make eosinophil proteins

  • Eosinophil: expresses eosinophil peroxidase

• This selective expression makes cells unique

How do immunologists define cells?

• Based on what proteins they make/express

• Especially focus on cell surface proteins (easy to study)

• Example markers: Antibody, CD3

What does it mean if a cell is “positive” or “negative” for a protein?

• Positive (+): cell expresses that protein

• Negative (–): cell does not express that protein

• Example:

  • CD3+ cell = expresses CD3

  • Antibody+ cell = expresses antibody

How can protein expression help identify cell types?

Example:

• Antibody+ CD3– → B cell

• CD3+ Antibody– → T cell

Why does identifying immune cells feel confusing at first?

• Many types, lots of surface markers

• Not “obvious” at first glance

• That’s okay—it’s still early in learning (only lecture 3!)

What does “phenotype defines function” mean in immunology?

• What a cell makes determines what it does

What are “cell types” in immunology?

• Defined by proteins they make

• Example:

  • Antibody+ cell = B cell

  • CD3+ cell = T cell

• Cell type = overall lineage of a cell

What is a “cellular program” (or transcriptional program)?

• The complete set of proteins a cell makes

• Defines the function of that cell

What are “cell subtypes”?

• Subdivisions within a cell type, based on extra markers/proteins

• Example:

  • T cells → Helper T cell (CD4+) vs. Killer T cell (CD8+)

  • B cells → B1 vs. B2 subtypes

At the simplest level, what makes up the immune system?

• Cells (e.g., macrophage)

• Molecules (e.g., immunoglobulin/antibody)

How do immune cells achieve immunity?

• By interacting with:

  • Each other

  • Non-immune cells in tissues/their environment

• Through communication and exchange of signals

Do immune cells literally “talk” to each other?

• No — they communicate through molecular interactions

• Signals sent and received via proteins

How do cells communicate at the molecular level?

• Through receptors and ligands

  • Work like locks and keys

  • Example: Protein A (ligand) + Protein B (receptor) → click → change in cell behavior

• Leads to changes in gene expression

What are the two main ways cells communicate?

1. Direct communication – receptor on one cell binds directly to receptor/ligand on another cell

2. Indirect communication – via soluble mediators (e.g., cytokines)

Can any cell respond to any ligand?

• No — a cell can only respond if it has the matching receptor

• Receptor-ligand pairs = “cognate pairs”

**Review cognate for test

Why is the concept of “cognate pairs” important?

• Critical for antigen-specific responses in adaptive immunity

• Ensures that only the right cells respond to the right signals

How do receptor:ligand interactions change gene expression?

1. Receptor binds ligand → interaction begins

2. Triggers secondary messengers inside the cell

3. Secondary messengers activate transcription factors

4. Transcription factors enter nucleus

5. Cell transcribes & translates new products

Real example: How do cells respond to viral infection?

• Virus infects cell

• Viral DNA detected by immune receptors inside cell

• Secondary messengers move to nucleus → change transcription

• Infected cell expresses interferons

• Interferons signal to nearby cells = paracrine signalling

• Effect: “Stop transcribing” → limits viral replication

  • Stop virus from propagating by using host cell machinery

What are some major receptor functions & types?

• Detect pathogens → Pattern recognition receptors

• Receive soluble signals → Cytokine receptors

• Move/migrate → Chemokine receptors

• Stick to other cells/environment → Adhesion receptors

• Respond to cell-surface signals → Co-stimulatory receptors

• Sense mechanical force → Stretch receptors

• Bind antibodies → Fc receptors

*Table will not be on test

How did immunologists simplify receptor naming?

• Before: many competing names (e.g., “B cell stimulating factor 2” vs. “hepatocyte growth factor”)

• 1982 Paris → created CD system

  • Clusters of Differentiation (CDs) = standardized names

  • Example: CD1, CD2, CD3, CD4 …

• Today: Over 370 CD molecules identified

What does “CD” stand for in immunology?

• Cluster of Differentiation

• Also called “Classification Determinant”

• Standardized system for naming receptors/proteins on cells

What are cytokines?

• Secreted signaling molecules

• Greek: “cyto” = cell, “kine” = movement

• Definition: Molecules that signal and cause cells to move or change

How did immunologists standardize cytokine naming?

• Before: many competing names (e.g., “B cell stimulating factor 2” vs. “human growth factor”)

• 1979 Switzerland → created Interleukin system (IL)

  • “Inter” = between, “leukin” = leukocytes (immune cells)

  • Means: molecules that signal between immune cells

• Numbered system: IL-1, IL-2, IL-3, IL-4 … (~50 total)

Do interleukins signal only between immune cells?

• Originally defined as signals between leukocytes

• But actually → they also signal with non-immune cells