Pathology chapters
Antigens, antibodies and innate and acquired immunity
How the body defends itself: innate versus adaptive immunity, the cells involved (T cells, B cells, NK cells, macrophages, dendritic cells), antigens, haptens and MHC, the five antibody classes and what each does, and active versus passive immunity.
- Innate immunity is present from birth, fast and non-specific with no memory (skin, phagocytes, NK cells, complement); adaptive (acquired) immunity is specific, slower the first time and has memory, through B cells (antibodies: humoral) and T cells (cell-mediated).
- CD4 helper T cells recognise antigen on MHC class II (on antigen-presenting cells); CD8 cytotoxic T cells recognise antigen on MHC class I (on all nucleated cells) and kill virus-infected and tumour cells.
- IgG: most abundant, crosses the placenta, main antibody of the secondary response; IgM: first antibody, pentamer, best at fixing complement; IgA: in secretions and breast milk; IgE: allergy and worms (binds mast cells); IgD: B-cell receptor.
On this page
Overview
The immune system protects against microbes and cancer cells. It has two arms that work together:
| Feature | Innate immunity | Adaptive (acquired) immunity |
|---|---|---|
| Present | From birth | Develops after exposure |
| Speed | Immediate (minutes to hours) | Slower at first (days) |
| Specificity | Non-specific (recognises common microbial patterns through receptors such as toll-like receptors) | Highly specific for each antigen |
| Memory | None | Memory: faster, stronger response next time |
| Components | Skin and mucosa, phagocytes (neutrophils, macrophages), NK cells, complement, acute-phase proteins, interferons, fever, inflammation | B lymphocytes (antibodies) and T lymphocytes |
Adaptive immunity has two branches:
- Humoral immunity: B cells become plasma cells that secrete antibodies; mainly against extracellular microbes and toxins.
- Cell-mediated immunity: T cells; mainly against intracellular microbes (viruses, TB) and tumour cells; also graft rejection.
Cells of the immune system
| Cell | Marker | Role |
|---|---|---|
| Helper T cells | CD4 (also CD3) | Direct the immune response through cytokines; help B cells and macrophages |
| Cytotoxic T cells | CD8 (also CD3) | Kill virus-infected and tumour cells (perforin, granzymes) |
| Regulatory T cells | CD4, CD25, FOXP3 | Suppress responses; maintain tolerance |
| B cells | CD19, CD20, surface IgM and IgD | Make antibodies (as plasma cells); present antigen |
| NK (natural killer) cells | CD16, CD56 | Innate; kill cells that lack MHC class I (virus-infected, tumour cells) without prior sensitisation; antibody-dependent cell-mediated cytotoxicity |
| Macrophages | CD14 | Phagocytosis, antigen presentation, cytokines |
| Dendritic cells (Langerhans cells in skin) | (none commonly tested) | The most efficient antigen-presenting cells: start T-cell responses |
Helper T-cell subsets
- Th1: IFN-γ → activates macrophages; cell-mediated immunity, granulomas, delayed hypersensitivity.
- Th2: IL-4, IL-5, IL-13 → IgE, eosinophils; defence against helminths, allergy.
- Th17: IL-17 → neutrophil recruitment; some autoimmune diseases.
Lymphoid organs
- Primary: bone marrow (B cells mature) and thymus (T cells mature).
- Secondary: lymph nodes (B cells in follicles of the cortex, T cells in the paracortex), spleen (T cells in periarteriolar sheaths, B cells in follicles), MALT.
Antigens
- Antigen: a substance recognised by an antibody or T-cell receptor.
- Immunogen: an antigen that can trigger an immune response by itself. Good immunogens are large (above about 10 kDa), foreign and chemically complex; proteins are the best.
- Hapten: a small molecule that is antigenic but not immunogenic on its own; becomes immunogenic when bound to a carrier protein (for example penicillin binding to proteins in drug allergy).
- Epitope (antigenic determinant): the small part of an antigen bound by an antibody.
- Adjuvant: a substance that enhances the response to an antigen (aluminium salts in vaccines).
- T-dependent vs T-independent antigens: proteins need T-cell help and produce memory; polysaccharides (capsules) can stimulate B cells directly with little memory (why pure polysaccharide vaccines work poorly in children under 2; conjugate vaccines overcome this).
MHC (HLA) and antigen presentation
The major histocompatibility complex (called HLA in humans) is on chromosome 6. MHC molecules show peptide antigens to T cells.
| Feature | MHC class I | MHC class II |
|---|---|---|
| Genes | HLA-A, B, C | HLA-DR, DP, DQ |
| Found on | All nucleated cells (and platelets) | Antigen-presenting cells (dendritic cells, macrophages, B cells) |
| Presents | Endogenous (inside the cell, for example viral) peptides | Exogenous (taken in) peptides |
| Recognised by | CD8 cytotoxic T cells | CD4 helper T cells |
Rule of 8: CD4 × MHC 2 = 8; CD8 × MHC 1 = 8.
HLA associations include HLA-B27 with ankylosing spondylitis (and other seronegative spondyloarthropathies), HLA-DR3 and DR4 with type 1 diabetes, HLA-DR4 with rheumatoid arthritis.
Antibodies (immunoglobulins)
Each antibody has two heavy and two light chains joined by disulfide bonds.
- Fab (fragment antigen-binding): binds antigen; variable regions give specificity.
- Fc (fragment crystallisable): decides the class and its functions (binding to phagocytes, mast cells and complement; crossing the placenta).
| Class | Structure | Key features |
|---|---|---|
| IgG | Monomer | Most abundant in serum (about 75%); main antibody of the secondary response; crosses the placenta (newborn protection); opsonises; fixes complement; neutralises toxins |
| IgM | Pentamer (J chain) | First antibody in the primary response; largest; best complement activator and agglutinator; B-cell surface receptor; does not cross the placenta, so IgM in a newborn means fetal infection |
| IgA | Monomer in serum; dimer in secretions (J chain + secretory component) | Protects mucosal surfaces; in saliva, tears, gut and breast milk (colostrum); does not fix complement by the classical route |
| IgE | Monomer | Binds mast cells and basophils (Fc receptor); type I hypersensitivity (allergy); defence against helminths; lowest serum level |
| IgD | Monomer | B-cell surface receptor; function otherwise unclear |
IgG crosses the placenta. IgM comes first. IgA is in secretions and milk. IgE is for allergy and worms.
Primary vs secondary response
| Feature | Primary response | Secondary (anamnestic) response |
|---|---|---|
| Lag period | Longer (about 1–2 weeks) | Shorter (a few days) |
| Main antibody | IgM | IgG |
| Amount | Low | Much higher |
| Duration | Short | Long |
| Affinity | Lower | Higher (affinity maturation) |
This is why vaccines are given as booster doses.
Types of acquired immunity
| Type | Natural | Artificial |
|---|---|---|
| Active (own immune system makes antibodies; long-lasting, with memory; slow to develop) | Infection | Vaccination |
| Passive (ready-made antibodies; immediate but short-lived, no memory) | Maternal IgG across the placenta, IgA in breast milk | Immunoglobulins and antitoxins (tetanus immunoglobulin, rabies immunoglobulin, anti-snake venom) |
For example, after a dog bite, rabies immunoglobulin gives passive protection immediately, and the vaccine gives active protection that builds up over days.
Key cytokines
| Cytokine | Main source | Action |
|---|---|---|
| IL-1, TNF | Macrophages | Fever, inflammation, acute-phase response |
| IL-2 | T cells | T-cell growth |
| IL-4 | Th2 | Class switching to IgE; Th2 development |
| IL-5 | Th2 | Eosinophils; IgA |
| IL-6 | Macrophages | Acute-phase proteins, fever |
| IL-10, TGF-β | Regulatory T cells | Suppress immune responses |
| IL-12 | Macrophages, dendritic cells | Drives Th1 |
| IFN-γ | Th1, NK cells | Activates macrophages |
| IFN-α, IFN-β | Virus-infected cells | Antiviral state in nearby cells |
Expect: innate vs adaptive immunity, CD markers (CD4, CD8, CD19/20, CD16/56), Th1 vs Th2, hapten vs immunogen, MHC class I vs II and which T cells see them, HLA-B27, antibody structure (Fab, Fc), functions of each immunoglobulin class, primary vs secondary response, and active vs passive immunity with examples.
Quick revision
- Innate: fast, non-specific, no memory. Adaptive: specific, memory.
- B cells: humoral (antibodies). T cells: cell-mediated.
- CD4 + MHC II; CD8 + MHC I. NK cells kill cells lacking MHC I.
- Hapten needs a carrier protein to be immunogenic.
- IgG: most abundant, crosses placenta. IgM: first, pentamer. IgA: secretions, milk. IgE: allergy, worms.
- Primary response IgM; secondary response IgG, faster and stronger.
- Active: infection, vaccine. Passive: maternal antibodies, immunoglobulin injections.
Written by The House Job from standard pathology and immunology references (Robbins and Cotran Pathologic Basis of Disease is the book named in the UHS PGET syllabus).
FAQ
Which antibody crosses the placenta?
IgG is the only immunoglobulin that crosses the placenta.
Which antibody appears first in an infection?
IgM, in the primary immune response.
What is the difference between active and passive immunity?
Active immunity is made by the person's own immune system after infection or vaccination and lasts long; passive immunity is the transfer of ready-made antibodies, which works at once but fades within weeks to months.
What is a hapten?
A small molecule that can bind antibody but cannot trigger an immune response unless it is attached to a larger carrier protein.