adaptive immunity

PART 1: INTRODUCTION TO THE ADAPTIVE IMMUNE SYSTEM

Section 1: Overview of Adaptive Immunity (Page 1)

The adaptive immune system provides a highly specific, targeted response to pathogens. It has memory, allowing for a faster and stronger response upon re-exposure.

Key Cells of the Adaptive Immune System:

PART 2: RECOGNITION OF NON-SELF – THE MHC

Section 2: The Major Histocompatibility Complex (MHC) (Page 2)

The adaptive immune system needs to recognise pathogens and also cells that are foreign.

2.1. What is MHC?

• A complex that allows the body to differentiate between self and non-self.

• Everyone's MHC is unique (like a molecular fingerprint).

• MHC molecules display the antigenic contents of the cell on the cell surface.

2.2. Function of MHC:

• Presents antigens (protein fragments) from inside the cell on the cell surface.

• This allows immune cells (T cells) to "see" what is happening inside the cell.

• A crucial component that can initiate the immune cascade:

  • Induction of humoral response (antibodies)

  • B-cell activation

  • T-cell stimulation

2.3. Alternative Name:

• MHC is also known as HLA (Human Leukocyte Antigen) in humans.

Section 3: Which Cells Express MHC? (Page 3)

Section 4: MHC Presentation is a Continuous Process (Page 3)

• MHC presentation of peptides is a continual process – expressing the insides of the cell on the outside.

• If the cell starts making and expressing foreign molecules (e.g., viral proteins, tumour antigens), then it will express those too.

• This allows the immune system to constantly survey for infection or abnormal cells.

Section 5: Clinical Case – MHC Deficiency (Page 4)

Case Study:
A child was given a standard immunisation (BCG) and after 7 days presented at Great Ormond Street Hospital (GOSH) with severe ulceration at the site of injection.

• Cause: Unknown at the time, but believed to be an HLA-DR (MHC Class II) deficiency.

• Treatment: Interleukins (ILs) and Interferon-gamma (IFN-γ).

Clinical Significance:

• MHC deficiencies result in severe immunodeficiency.

• Patients cannot effectively present antigens to T cells, leading to susceptibility to infections and adverse reactions to live vaccines (like BCG).

Courtesy of Prof P Brogan, Great Ormond Street Hospital

Section 6: Transplant Immunology – MHC (Dis)similarity (Page 5)

• Because all nucleated cells express MHC Class I, the host T cell receptor can recognise non-self MHCs.

• This recognition is called allorecognition.

• MHC mismatch between donor and recipient is the primary cause of transplant rejection.

Section 7: Limited MHC Diversity in Some Species (Page 5)

Some species have very limited MHC diversity due to inbreeding or population bottlenecks:

Clinical Significance: Limited MHC diversity makes populations more vulnerable to infectious diseases, as there is less variation in immune response capabilities.

PART 3: ANTIGENS

Section 8: What are Antigens? (Page 6)

Definition:

• Antigens are molecules presented on an MHC that initiate the adaptive immune response.

Source of Antigens:
All internalised peptides (antigens) are presented on surface molecules on the cell (MHC).

Two Sources of Antigens Presented on MHC:

• When the antigen is eliminated, the adaptive immune responses switch off.

PART 4: RECOGNITION OF ANTIGENS BY LYMPHOCYTES

Section 9: Which Cells/Molecules Recognise Antigens on MHC? (Page 7)

Section 10: Clonal Selection – The Key Principle (Page 8)

• Each lymphocyte is genetically programmed to recognise one specific antigen.

• Lymphocytes specific for any given antigen are only a tiny proportion (perhaps 1 in 100,000 to 1 in 1,000,000) of all the lymphocytes present.

• Once an antigen is bound, the specific lymphocyte proliferates rapidly (clonal expansion) to generate a large population of effector cells.

Illustrative Example (Page 8):

This demonstrates the power of clonal selection and expansion – a tiny number of specific cells can generate a massive, effective response.

PART 5: T CELL DIFFERENTIATION AND ACTIVATION

Section 11: Linear Differentiation of T Cells (Page 9)

T cells differentiate into two main types:

Section 12: Getting Started – The Two Signals for T Cell Activation (Page 9)

Pathogen eradication is a stepwise process. Adaptive immunity cannot work without the innate immune system that generally detects the pathogen first.

Requirements for T Cell Activation:

1. Signal 1 – Antigen Recognition:

   • Lymphocyte has to recognise that a cell is either non-self OR contains elements of non-self presented on MHC.

   • Source of antigen:

     • Through phagocytosis → presented on MHC Class II

     • Through infection → presented on MHC Class I

2. Signal 2 – Co-stimulation:

   • Provided by innate immune cells (dendritic cells, macrophages) that have recognised PAMPs.

   • This ensures that T cells are only activated in the context of a real infection (prevents autoimmunity).

Section 13: Activation of T Helper Cells (Page 10)

Once activated, T helper cells (CD4+) stimulate:

• Cytotoxic T cells (CD8+) – to kill infected cells

• B cells – to produce antibodies

SUMMARY TABLE: ADAPTIVE IMMUNITY KEY CONCEPTS