Immunology Made Simple

1. Spleen

1. Location and Immune Response

• LUQ (Left Upper Quadrant):
  • Location of the spleen.
• Beta and T Cells:
  • Beta cells: Located in the pancreas (in the islets of Langerhans) and involved in insulin production.
  • T cells: Part of the immune system, involved in adaptive immunity.

2. Infectious Mononucleosis:

• Cause:
  • Epstein-Barr Virus (EBV).
• Clinical Features:
  • Splenomegaly: Enlargement of the spleen due to infection.
  • T-cell Hyperplasia: An increase in T cells as part of the immune response to the viral infection.

2. Thymus

1. Origin:
   • Derived from the 3rd pharyngeal pouch.
2. Function:
   • Responsible for the maturation of T-cells.
   • T-cells are made in the bone marrow, but they mature in the thymus.
3. Congenital Absence:
   • If the 3rd pharyngeal pouch is absent, it leads to DiGeorge Syndrome, a condition where the thymus is underdeveloped or absent, affecting immune function and causing antibody deficiencies.

3. Antibodies and Immune Responses

Antibody	Function	Characteristics
IgG	– Secondary immune response – Crosses the placenta – Complement fixation – Opsonization – More in plasma	– Main antibody in secondary immune response – Helps fix complement and aids in opsonization – Crosses placenta to provide passive immunity
IgA	– Present in secretions (saliva, mucus, breast milk) – More produced but drains	– Found in mucosal membranes – Lower concentration in blood but crucial for mucosal immunity
IgE	– Involved in HSR-1 (Type I hypersensitivity) – Plays a role in parasitic infections	– Involved in allergic reactions and parasite defense – Elevated in parasitic infections and allergies
IgM	– Primary immune response – Fixes complement – Pentameric structure	– First antibody produced during primary response – Fixes complement and activates immune response

4. Types of Grafts

Graft Type	Definition	Example
Autograft	Graft taken from the same body	Skin graft from one part of the body to another part of the same body
Isograft	Graft between identical twins (genetically identical)	Organ transplant between identical twins
Allograft	Graft between individuals of the same species	Kidney transplant between non-identical humans
Xenograft	Graft between individuals of different species	Heart valve transplant from a pig to a human

5. Transplant Rejection

Type of Rejection	Timeframe	Description
Acute Rejection	Occurs within weeks to months	– The immune system attacks the transplanted organ shortly after the transplant.
Chronic Rejection	Occurs within months to years	– Long-term rejection that leads to gradual deterioration of the transplanted organ over time.
Hyperacute Rejection	Occurs within minutes	– Immediate rejection, often due to pre-existing antibodies against the donor tissue, resulting in rapid organ failure.

6. HSR-I (Type I Hypersensitivity Reaction)

Type of Hypersensitivity	Mechanism	Details
HSR-I (Type I)	IgE-mediated	– Genetic predisposition (atopy). – Mast cells release histamine upon activation by IgE. – Conditions: Severe anaphylaxis, asthma, atopic dermatitis, allergic rhinitis.
HSR-II (Type II)	Antigen + Antibody Complex → Cell damage	– IgG or IgM antibodies bind to antigens on the cell surface, leading to cell damage (e.g., hemolytic anemia, autoimmune diseases).
HSR-III (Type III)	Antigen + Antibody + Complement Activation	– Formation of immune complexes, leading to complement activation and tissue damage (e.g., in lupus, rheumatoid arthritis).
HSR-IV (Type IV)	T-cell Mediated	– T-cell mediated immune response causes tissue damage (e.g., in contact dermatitis, tuberculosis, graft rejection).

7. Complement System

• Helps to reduce infection.
• Group of 20 proteins.
• Proteins are inactive, become active during infection.
• 11 proteins are important.
• Each complement protein has 2 components.
  • Example: C1 → C1a, C1b.
• Linked with T-cell mediated hypersensitivity type IV.

1. Pathways of Activation

• Classical pathway → triggered by IgG or IgM.
• Alternative pathway → triggered directly by microbial surfaces.
• Mannose-binding lectin pathway → triggered by mannose residues on microbes.

2. Important Functions

• Opsonization → C3b coats microbes, enhances phagocytosis.
• Chemotaxis → C5a attracts neutrophils.
• Membrane Attack Complex (MAC) → C5b, C6, C7, C8, C9 assemble and lyse microbes.

3. Deficiency States

• C5–C9 deficiency → recurrent Neisseria bacteremia.
• C1–C6 deficiency → recurrent pyogenic infections (pus-forming bacteria), ↑ risk of SLE.

4. Adaptive Immunity Link

• B-cell maturation → Plasma cells → Antibody production → Humoral immunity.
• T-cells → Cell-mediated immunity.
  • CD4 (Helper T cells) → Support humoral immunity.
  • CD8 (Cytotoxic T cells) → Directly kill infected cells.

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5. Innate Immunity

• No memory, acts immediately and non-specifically.
• Components:
  • Physical barriers (skin, mucosa).
  • Cells: Neutrophils, Macrophages, NK cells.
  • Proteins: Complement system, acute phase proteins.

6. Adaptive Immunity

• Specific response develops memory.
• Components:
  • B-cells → mature into plasma cells → produce antibodies.
  • T-cells → CD4 (helper) and CD8 (cytotoxic).
• Basis of therapeutic monoclonal antibodies.

1. Monoclonal Antibodies (Examples)

Drug	Target	Use
Denosumab	RANK-L	Osteoporosis
Omalizumab	IgE	Asthma (allergic)
Palivizumab	RSV F protein	RSV bronchiolitis prophylaxis
Eculizumab	C5 complement	Paroxysmal nocturnal hemoglobinuria (PNH)
Efalizumab	CD11a (LFA-1)	Psoriasis
Natalizumab	α4-integrin	Multiple sclerosis
Trastuzumab	HER2/neu receptor	HER2+ breast cancer, gastric cancer

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