Here are the notes for Unit 4 — exam-ready! 📝

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UNIT 4 – Notes

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✍️ Question 1: Describe the Structure and Functions of MHC Antigens.

Introduction:

The Major Histocompatibility Complex (MHC) is a large genomic region that encodes cell surface proteins essential for the immune system to recognize foreign substances. In humans, MHC is called the HLA (Human Leukocyte Antigen) system, located on chromosome 6.

Structure of MHC:

MHC Class I:

• Present on all nucleated cells of the body
• Structure: One α (alpha) chain + β2 microglobulin
• The α chain has 3 domains: α1, α2 (peptide binding), α3 (transmembrane)
• Binds peptides of 8–10 amino acids
• Presents antigens to CD8+ cytotoxic T lymphocytes

MHC Class II:

• Present only on Antigen Presenting Cells (APCs) — macrophages, dendritic cells, B cells
• Structure: One α chain + one β chain (both transmembrane)
• Peptide binding groove formed by α1 + β1 domains
• Binds peptides of 13–25 amino acids
• Presents antigens to CD4+ helper T lymphocytes

Functions of MHC:

1. Antigen Presentation – Presents processed peptides to T cells
2. Self vs Non-self Recognition – Helps immune system identify foreign cells
3. Immune Regulation – Controls the type of immune response
4. Role in Transplantation – MHC mismatch leads to graft rejection
5. T cell Development – Required for positive and negative selection in thymus

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✍️ Question 2: Write a Note on HLA System.

Introduction:

HLA (Human Leukocyte Antigen) system is the human version of MHC. It is encoded by genes on the short arm of chromosome 6 and plays a crucial role in immune recognition and transplantation.

HLA Loci:

Class	Loci
Class I	HLA-A, HLA-B, HLA-C
Class II	HLA-DR, HLA-DP, HLA-DQ
Class III	Complement proteins (C2, C4)

Importance of HLA:

1. Tissue Typing – HLA matching is done before organ transplantation to prevent rejection
2. Disease Association – Certain HLA types are linked to diseases:
   • HLA-B27 → Ankylosing spondylitis
   • HLA-DR3/DR4 → Type 1 Diabetes
3. Paternity Testing – HLA typing used in forensic science
4. Blood Transfusion – HLA matching reduces transfusion reactions

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✍️ Question 3: Explain the Types of Transplants and Mechanism of Graft Acceptance and Rejection.

Introduction:

Transplantation is the process of transferring an organ or tissue from one individual (donor) to another (recipient). The immune system plays a major role in graft acceptance or rejection.

Types of Transplants (Grafts):

Type	Donor → Recipient	Example
Autograft	Self → Self	Skin graft from patient's own thigh
Isograft	Identical twin → Twin	Kidney from identical twin
Allograft	Same species, different individual	Cadaver kidney transplant
Xenograft	Different species → Human	Pig heart valve to human

Mechanism of Graft Acceptance:

• Close HLA matching between donor and recipient
• Use of immunosuppressive drugs (cyclosporine, steroids)
• Regulatory T cells suppress immune attack
• No pre-formed antibodies against donor antigens

Mechanism of Graft Rejection:

Types of Rejection:

Type	Onset	Mechanism
Hyperacute	Minutes to hours	Pre-formed antibodies against donor ABO/HLA antigens → complement activation → vessel blockage
Acute	Days to weeks	CD4+ and CD8+ T cells recognize donor MHC → direct cytotoxicity
Chronic	Months to years	Slow antibody-mediated + T cell-mediated damage to graft vessels

Steps in Acute Rejection:

1. Host APCs process donor antigens
2. CD4+ T helper cells activate and release cytokines (IL-2, IFN-γ)
3. CD8+ cytotoxic T cells are activated
4. CTLs attack and destroy graft cells via perforin and granzyme
5. Macrophages cause inflammation and tissue damage

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✍️ Question 4: Describe Tumour Specific Antigens and Immune Response to Tumour.

Introduction:

Tumour immunology studies how the immune system recognizes and responds to cancerous cells. Tumour cells express unique antigens that can be targeted by the immune system.

Tumour Antigens:

1. Tumour Specific Antigens (TSA):

• Found only on tumour cells, absent on normal cells
• Caused by gene mutations
• Examples: mutated p53 protein, viral antigens (HPV E6/E7 in cervical cancer)

2. Tumour Associated Antigens (TAA):

• Present on tumour cells and some normal cells (overexpressed)
• Examples:
  • CEA (Carcinoembryonic Antigen) – colon cancer
  • AFP (Alpha-fetoprotein) – liver cancer
  • PSA (Prostate Specific Antigen) – prostate cancer

Immune Response to Tumour:

Immune Component	Action
NK Cells	Kill tumour cells without MHC — first line defence
CD8+ CTLs	Recognize TSA on MHC I → kill via perforin/granzyme
CD4+ T cells	Activate macrophages and CTLs via cytokines
Macrophages	Phagocytosis + produce TNF-α to kill tumour cells
Antibodies	ADCC (Antibody Dependent Cell Cytotoxicity)

Tumour Immune Evasion Mechanisms:

1. Reduced MHC I expression – T cells can't recognize tumour
2. Immunosuppressive cytokines – IL-10, TGF-β suppress immune cells
3. T cell exhaustion – Chronic antigen exposure weakens T cells
4. PD-L1 expression – Tumour cells switch off T cells
5. Antigen loss variants – Tumour mutates to lose TSA

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⭐ Quick Revision Box:

Topic	Key Point
MHC I	All nucleated cells → CD8+ T cells
MHC II	APCs only → CD4+ T cells
HLA	Chromosome 6, tissue typing
Autograft	No rejection
Xenograft	Highest rejection risk
Hyperacute rejection	Pre-formed antibodies
NK cells	Kill tumour WITHOUT MHC
TSA	Only on tumour cells