4.1a Immunity

PATHOLOGY SPECIFIC NOTES - Why are you lazy? Read the whole thing you’re better off. Well, choice is an illusion

Immunity is divided into

  • Innante
    • Non-specific
    • No memory (amnesic)
  • Adaptive
    • specific
    • Memory (a-amnesic)

Innate Immunity

Innate immunity is the inborn resistance against infections that an individual possesses right from the birth, due to his genetic or constitutional makeup.

  • Barriers

    • Anatomical [skin]
    • Physiological [Secretions and their contents]
  • Proteins

    • C-reactive proteins
    • Lectin
      • e.g: Mannose Binding Lectins [CD14 of macrophage recognizes]
    • Complement proteins
    • Surfactants and plasma proteins
  • Cells

    • Neutrophils
    • Macrophages
    • NK Cells
      • Natural Killer (NK) Cells are lymphocytes in the same family as T and B cells, coming from a common progenitor. However, as cells of the innate immune system, NK cells are classified as group I Innate Lymphocytes (ILCs) and respond quickly to a wide variety of pathological challenges.
      • They kill virus infected cells
      • Kills tumor cells

How are pathogens recognized?

Pattern Recognition receptors

  • Bacteria:
    • Pathogen/Microbe Associated Molecular Patterns
  • Inflammation
    • Damage Associated Molecular Patterns


  • Toll-like receptor
    • Causes activation of
      • NF-NF-κB(Nuclear factor kappa-light-chain-enhancer of activated B cell - a transcription factor)
        • Causes recruitment of leukocytes
        • Activates COX-2
      • IFN-1 (type 1)
        • Antiviral action ]
  • C-type LR (Lectin Receptor)
    • Important against fungal infections

Cytosolic Receptors

  • RIG-like receptor
    • Act against viral nucleic acids
  • NOD-like receptor
    • Identifies:
      • Bacteria
      • K+ levels (eflux)
      • Uric Acid
      • ROS
    • Activates inflammasome
      • Which activates Caspase 1 -> IL1 -> Fever Inflammation


This is a component of Innate Immunity

Hematopoitic Stem Cells -> Lymphoid Stem Cells

  • Lymphoid Stem Cells then differentiates
    • In Thymus gland: T cell
    • In Bone Marrow: B-Cell
    • Naive: Natural Killer Cells
      • Innate Lymphoid Cells


  • They can secrete cytokines like T-cells
  • They do not have TCR
  • They were earlier known as Large Granular Lymphocytes [LGL]
  • They kill virus infected cells
  • Kills tumor cells

[[Pasted image 20210708230309.png]]

Two important receptors

  • Stimulatory/Activating receptor
  • Inhibitory Receptor
    • All cells in the body have MHC Class I molecule
    • This stimulates the inhibitory receptor
  • MHC class I has reduced expression in mutated cells (tumors) or viruses
  • Virus and cancer tumors have molecules that amplify molecules that activate the Activating receptor

NK cells also have

  • CD16
    • Also known as Fc receptor
    • Fc portion of the ImmunoglobulinG attaches to this
      • NK-cell destroys the coated antigenic cell
      • Antibody Dependent Cell Mediated Cytotoxicity [CDCC]
  • CD56

Adaptive Immunity

  • specific
  • Memory (a-amnesic)
  • Contributed by
    • T-cells - Cell-mediated
      • Effective against intracellular microbeszb
    • B-Cells - Humoral immunity
      • Effective against extracellular microbes


  • Located in the

    • Lymph node
    • Spleen
    • GIT
      • Mucosa Associated Lymphoid Tissue MALT
        • Present highly in the Peyer’s patches of the Ileum
      • Enteric fever is due to the ulceration of Peyer Patches and thus commonly it’s in the ileum
    • Tonsils
  • The lymph node has muliple zones

    • Cortex - B Cells
    • Paracortex - T-cells
    • Medulla Macrophages

[[Pasted image 20210707215520.png]]

B-Cell markers

CD stands for Cluster of Differentiation

  • CD 19 to 23 (1923)
    • CD19 - Pan B Marker (present in all stages of B-cell development)
    • CD21 - Receptor for EBV (Epstein Barr Virus)
  • CD 40
    • CD40 ligand is expressed on the T-cells
      • CD40L of T-cell and CD40
      • B-cell : T-cell interaction
      • Important in production of high quality antibody formation
  • CD80 / B7-1 CD86 / B7-2
    • CD80/86 are known as the B7 (B7-1 and B7-2 respectively)
      • These interact with CD28 on the T-cell to produce co-stimulatory signal

B-cells on activation -> Plasma-cell

  • Plasma cells secrete antibodies (immunoglobulins)


[[Pasted image 20210707220953.png]]

Made up of:

  • Light Chains
    • λ (lambda)
    • κ (kappa)
  • Normal ratio : 3:1 to 3:2 κ:λ
  • Heavy Chains
    • α (alpha)
    • γ (gamma)
    • δ (delta)
    • ε (epsilon)
    • μ (mu)
  • Isotype
    • Different classes of antibodies in the same person
  • Allotype
    • Difference in antibody taken from two people
  • Idiotype
    • Variable part of antibody is different in same person

Immunoglobulin Classes / Isotypes

  • These are dependent upon the heavy Chains present


  • Presence of Gamma γ heavy chain
    • Maxiumum concentration
    • Crosses Placenta
    • Complement Activation
    • Opsonization


  • Presence of the Alpha heavy chain
    • Forms:
      • Monomer in the Serum
      • Dimer in the Mucosa and Secretions - joined by J joining chain
  • First Line of Defense (as majority of the infections have to pass through mucosal layer)
    • It activates the Alternate pathway rarely


  • Presence of mu heavy chain
  • M for
    • Max Size
      • Pentameric
    • Max Molecular Weight
  • Complement Pathway Activation
    • Primary Immune Response - IgM is mostly produced than IgG (predominant)
  • Monomeric form is present on B-Cell Receptor


  • Presence of Delta Heavy Chain
  • Functions as acts as B-cell receptor


  • Presence of Epsilon Heavy Chain
  • Lowest Concentration
  • Attached to the surface of Mast Cells
    • Responsible for Type-1 Hypersensitivity Reaction
  • Heat labile antibody


  • Exogenous
  • Endogenous
  • Autogenous
Types of Antigens based on B-Cell activation
Proteinaceous/T-Cell Dependent

Non-Proteinaceous Antigens

  • These are free antigens that do not require any additional cells for activation
    • Thus also known as thymic-independent antigens/T-cell independent
    • Pentameric IgM antibodies are produced when bound to monomeric form of IgM present on BCR
  • Leads to T-cell indepent activation of B-Cell

[[Pasted image 20210707224227.png]]

Proteinaceous Antigens

  • Requires the support of T-CeLLS for proper activation of Immune System

[[Pasted image 20210707224246.png]]

  • B-Cell or APCs (antigen presenting cells) expresses antigen on the surface
  • T-CR (T-cell receptor) then recognizes the antigen
  • T-cell then attaches to the MHC class
  • CD40(B-cell) and CD40L (T-Cell) interaction occurs
    • This leads to secretion of IL-4/IL-5
    • Cytokine Reference
    • This causes IgM -> IgG/A/E [isotype/class switching : change in heavy chain by IL-4/IL-5]
      • This is reaaallyy important for somatic hypermutation ^4e39b6
      • If this is cytokine secretion is blocked -> Hyper IgM syndrome

T Cell

  • Named from the fact that they develop in the thymus
  • Present in the
    • Lymph Node

      • Paracortex

      [[Pasted image 20210707215520.png]]

    • Spleen

      • Periarteiloar Lymphoid Sheath
        • PALS
    • GIT

      • Present within the intraepithelial lymphocytes [IELs] | compare this with B cells in the mucosal lymph node (MALTS)


  • T-cell Receptor (TCR)
    • Binds to prebound antigens only
    • Prebound antigens are presented by APCs
  • CD molecules
    • CD 1 to 5, 7 and 8 [CD1 CD2 CD3 CD4 CD5 CD7 CD8]
      • These are all T-cell markers
      • Pan-T-Cell Marker - CD3
        • Significant in signal transduction mechanism
        • Activation of T-cell assisted by calcineurin and IL-2
    • CD28
      • Costimulatory signal from APCs such as B-cells
      • Binds to Ce
    • CD40-L
      • Attaches to B-Cell CD40 receptor
      • Important for T-Cell B-Cell

T-Cells can be divided into:

  • CD4+ T Cells - Helper Cells
    • CD4 molecule is present

    • Subtypes

      T Cell typeReactionSecretion of
      Th1Type IV HRIL2 and IFN gamma
      Th2Type I HRIL-4 and IL-5
      Th17Responsible for Fungal infections and autoimmune disordersIL-17

  • CD+ T-cells - Cytotoxic
    • CD8 positive
    • Binds to MHC Class I

| CD4:CD8 | 2:1 | | —–– | — |

Activation of Immune System

  • Antigens are divided into
  • Proteinaceous antigens

    • T-Cell dependent
  • Carbohydrate/Lipid Antigens (non-proteinaceous)

    • T-Cell independent
  • Antigen presenting cells internalize antigens and process it

  • APCs then express the antigenic peptide through the MHC molecule

  • MHC molecule is responsible for attachment of antigenic peptide

  • Then APCs enter the systemic circulation and lymphatic circulation

  • Clonal Selection occurs:

    • Only a few T-cells come in contact with specific antigen peptides presented by the APC depending upon the specific antigen


  • Effector T-cells
    • Deals with the presentation
  • Memory T-cells
    • These remain dormant after developing antigen receptor
    • Deals with later infection
    • These are fewer in number
    • CD45RO is used to detect memory T-Cell
      • CD45 is present on leukocytes
      • Mem OR y - Memory device


  • APCs internalize internal/external peptides (after being broken down)
  • The MHC chains produced by the Endoplasmic Reticulum is expressed on the APC surface along with the peptide in

Professional APCs

  • These APCs have a very high expression of MHC 1
  • Dendritic Cells

    • Langerhans cells (tissue resident macrophage) - Skin and Interstitial Cell
    • Follicular dendritic cells - reservoir for HIV present in - Lymph node and spleen
  • B-Cells

    • Activated B-cells turn into plasma cells -> secrete antibodies
  • Macrophages

    [[Pasted image 20210701093452.png]]

    • CD13, CD14, CD15 and CD33 are CD markers

Non-Professional APCs

  • These are non-standard APCs with low but significant expression of MHC
  • Fibroblasts
  • Endothelia Cells
  • Thymic epithelial cells
  • Glial Cells
  • Pancreatic Beta-Cells


Major Histocompaitibility Complex Also known as HLA - Human Leukocyte Antigen

  • The gene encoding is present on short arm of Chromosome 6p [[Pasted image 20210710123112.png]]
  • Class I region codes for MHC I
    • MHC I is present in all nucleated cells and Platelets
  • Class II region encodes for MHC II
    • MHC II is present in all APCs
  • Class III region codes for
    • C2
    • C4
    • Properdin
    • TNF-alpha
    • 21-alpha hydroxylase
  • Cell Activated - immune cell activated
  • Ag Binding Cleft

MHC Class I

  • Made of 3 alpha chains and 1 beta chain
  • Antigenic cleft is present in between alpha 1 and alpha 2
  • Alpha 1 and alpha 2 are distal alpha chains
  • Alpha 3 is proximal alpha chain

Distal chains form the antigen binding cleft

  • CD8+ T-cells bind to MHC Class I - Endogenous Antigens

MHC Class II

  • Made of two alpha and two beta
  • Antigenic cleft is present in between Beta 1 and Alpha 1
  • Beta 1 and Alpha 1 are distal chains
  • MHC Class I is detected by Alloantiserum
  • MHC Class II is detected by Mixed Lymphpcyte Reaction
  • CD4+ T-cells bind to MHC Class II - Exogenous Antigens
  • Most antigens bind to MHC class II

Clinical Relevance Of MHC

  • Genetic Association of Disease
    • HLA - DR3/DR4 of class II region is associated with Type 1 Diabetes Melitus 2
    • HLA - B27 of Class I region is associated with Ankylosing spondytis 3
  • Organ Transplantation
    • Gene match of HLA is done to ensure compaitibility
    • Tissue typing is done by:
      • Mixed Lymphocyte Reaction (the same test for MHC II)
      • Micro-cytotoxicity assay
      • Nowadays HLA molecular matching is done
  • Paternity Disputes

T-Cell Activation

  • There are 2 signals involved
    • Primary Signal/Signal 1
      • MHC II binding to CD4 receptor
    • Co-stimulatory signal
      • CD28 on T cell with B7
        • B7a - CD80
        • B7b - CD86
    • Both signals are required for T-cell activation

      • External antigen provides both signals
      • Self antigens however only provide primary signal
        • Co-stimulatory signal is not generated - ANERGY
        • This property is known as: Tolerance is exhibited by Self-antigens
    • Negative co-stimulatory signal may also be received

      • Negative co-stimulatory signal delivery molecules - usually present in self-antigens
      • It reduces T-cell activation
        • CDLA-4
        • PD-1
      • B7.1 and B7.2 interact with this
Major Histocompaitibility Complex
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