Fundamentals of the Immune System

Immunology

The study of host responses to non-self (and dysregulated self like autoimmunity).

Three lines of defense

Barriers, innate immunity, adaptive immunity.

Example of a physical barrier

Intact skin.

Example of a mucosal barrier site

Oral, intestinal, or respiratory mucosa.

Two biochemical barrier factors

Tears and mucus.

Antimicrobial enzymes/peptides at barriers

Lysozyme, defensins, cathelicidins.

Innate response speed and specificity

Fast and non-specific; no memory.

Adaptive response speed and memory

Slower on first exposure; has memory.

What drives innate recognition

Pattern-recognition receptors (PRRs) that bind PAMPs.

What creates adaptive receptor diversity

Gene rearrangements in TCRs and BCRs.

Key innate cellular players (one example)

Neutrophils (phagocytes).

Another innate cell example

Macrophages (phagocytose and present antigen).

One more innate cell example

Mast cells (mediate inflammation).

Key soluble innate mediators

Complement, cytokines, lysozyme.

Main goals of inflammation

Deliver cells/mediators, eliminate agents, repair tissue, clear debris.

What do PRRs bind

Pathogen-associated molecular patterns (PAMPs).

High-level complement definition

Cytokines

Secreted signals that coordinate immune cells.

Antibodies

Specifically bind antigens to help remove them.

Two uptake mechanisms for extracellular material

Phagocytosis and pinocytosis.

Opsonin

A molecule that coats targets to enhance uptake.

Two opsonin examples

Complement fragments and lectins.

One receptor type that binds opsonins

Fc receptors (also complement, scavenger, dectin receptors).

Beyond uptake, what does phagocytosis trigger

Cell activation/maturation and migration to lymph nodes.

How does phagocytosis improve T-cell activation

Up-regulates MHC and cytokine expression.

Three broad functional immune cell groups

APCs, lymphocytes, effector cells.

APCs

Dendritic cells.

Lymphocytes

B cells and T cells.

Effector cells

Activated T cells or granulocytes.

CD

Cluster of differentiation (surface markers).

Universal leukocyte CD marker

CD45.

What does a + mean after a CD marker

That marker is present on the cell.

APC markers to know

CD11+, CD14+.

Best cell at initiating T-cell responses

Dendritic cells.

B-cell hallmark markers

CD19+, CD20+.

Plasma cell marker

CD138+.

T-cell pan-marker

CD3+.

CD4+ T cells

Helper function (coordinate immune responses).

CD8+ T cells

Cytotoxic killing of infected/tumor cells.

NK cells

What's distinctive?

Granulocyte markers

CD15+, CD33+.

Three granulocyte types

Neutrophils, eosinophils, basophils (mast cells in tissues).

Neutrophils typical blood %

~50-70% of WBCs.

Neutrophils two key functions

Phagocytosis and degranulation/NETs.

Eosinophils core roles

Anti-parasite and allergy.

Basophils/mast cells core roles

Inflammation, allergy, anti-parasite; histamine-rich granules.

How does innate link to adaptive?

Innate processing peptide presentation on MHC.

Which cells read MHC and respond?

CD4 and CD8 T cells.

What is humoral immunity?

Antibody-mediated protection by B-cell products.

What is cell-mediated immunity?

Protection by cytotoxic T cells and macrophages.

What is active immunity?

Your own immune response (infection or vaccination) memory.

What is passive immunity?

Preformed antibodies (maternal/therapeutic) immediate, temporary.

Name the 3 complement activation pathways.

Classical, alternative, lectin.

One shared endpoint of all pathways?

Formation of the membrane attack complex (MAC).

A central opsonin from complement

C3b.

Common complement-driven inflammatory mediators

C3a and C5a.

First step when a pathogen tries to enter?

Barriers block entry.

If barriers fail, what detects microbes?

Innate PRRs sense PAMPs.

What immediate processes follow detection?

Phagocytosis, complement activation, inflammation.

How is antigen info handed to adaptive immunity?

Peptides are presented on MHC to T cells.

Which adaptive cells execute responses?

CD4 help for B cells/CD8; CD8 kill infected cells.

What remains after clearance for faster future responses?

Immunologic memory.