2. INTRODUCTION
• IMMUNITY:
1. Defined as resistance offered by host against microorganisms/ foreign substances.
2. It is of 2 types:
• Innate immunity and
• Acquired immunity.
3.
4. Immune response :
• Refers to highly coordinated reactions developed by cells of immune system in host to
primarily protect the host from harmful pathogens or foreign substances.
• It is of 2 types:
• Antibody (humoral) mediated immune response (AMI):
• protects from extracellular pathogens by secreting antibodies that binds and neutralizes antigens
circulating in extracellular space.
• Cell- mediated immune response(CMI):
• protects against intracellular pathogens by various effector cells such as macrophages, natural
5. CMI AND AMI ARE INTERDEPENDENT!!
• Highly dependent on each other.
• Cytokines released from T- cells stimulate B- cells for antibody production.
• Many effector cells like NK cells, macrophages use Ab as receptors to recognise
target cells for killing.
• Common initial events takes place before induction of either of immune responses
i.e:
1. Antigen presentation to helper T- cells.
2. Activation and Differentiation of helper T- cells into either TH-1 or TH-2 subsets.
6. 1. ANTIGEN PRESENTATION
• For induction of immune response, recognition of antigens by T cells is essential; antigen is
processed into smaller antigenic peptides containing specific epitopes which are combined with
MHC molecules (class I or II) and presented on the host cell surface.
1. ANTIGEN PRESENTING CELLS : cells that present antigenic peptide along MHC class II to TH
cells (dendritic cells, macrophages).
2. TARGET CELLS: cells that present antigenic peptides along MHC class I to TC cells (virus infected
/tumor).
7. ANTIGEN PROCESSING PATHWAYS:
1. CYTOSOLIC PATHWAYS:
• Intracellular antigens are processed (tumour cells).
• Presented with MHC-1 to cytotoxic T- cells.
2. ENDOCYSTIC PATHWAYS:
• Extracellular antigens are processed (toxins).
• Presented with MHC- II to helper T- Cells.
8. 2. a) Activation of helper t -cells
1. Signal Generation:
3 specific signals:
a) Antigen specific signal
b) Co stimulatory signal
c) Cytokines signal
2. Signal Transduction:
• Initiated at CD4 molecule interacting
with CD 3 complex
Activation of helper T- cells
9. 2. b) differentiation of helper t -cells
• Activated T helper cells secrete increased amount of IL-2 and IL-2 receptors (IL2R OR CD25 ).
• IL-2 binds to its receptors on T helper cells and also on other T helper cells and induces naïve T cells to proliferate and
differentiate.
• Activated T helper cells becomes lymphoblast cells and differentiating into memory and effector t helper cells.
EFFECTOR T HELPER CELLS –
• Derived either naïve T helper cells or pre-existing memory T helper cells .
• Further differentiates into T helper 1 and T helper 2 subsets and secrete cytokines which has prime role in immune response.
MEMORY T HELPER CELLS –
• Derived from activated TH cells.
10.
11. CELL- MEDIATED IMMUNE RESPONSE
EFFECTOR CELLS OF CMI:
• Mediated by antigen specific/ nonspecific effector cells, function performed by direct killing of the target
cells.
• Important mediator of CMI is antigen specific cytotoxic T cells along with macrophages ,NK cells ,
neutrophils , and eosinophils .
1. CYTOTOXIC T- LYMPHOCYTES –
o Naïve t- cells respond to tumor antigens processed and presented along MHC-1 which secretes cytotoxic
enzymes (Perforins and Granzymes) to lyse target cell.
2. NATURAL KILLER CELLS –
o Act as first line of defense.
o No MHC restriction and no memory.
12. Mechanism of nk cell- mediated cytotoxicity
• Receptor Interaction:
1. Activation receptor: NKR-P1 CD-16.
2. Inhibitory receptor: C- type inhibitory receptors.
• Target Cell Destruction:
1. Cell lysis like cytotoxic T cells via perforins and
granzymes.
2. Antibody-dependent cell- mediated cytotoxicity.
13. ASSESSMENT/ DETECTION OF CMI
• Mixed lymphocytes reactions : In- vitro system for assaying T- cell proliferation.
• Cell – mediated lympholysis: In- vitro assay to test cytotoxic function of effector cell.
• Graft vs Host reaction: In- vivo system for cell mediated cytotoxicity.
14. ANTIBODY/ HUMORAL MEDIATED IMMUNE RESPONSE
• Protects host by secreting antibodies by preventing
microbes invasion present on host cell surface.
• 3. Sequential steps :
1. Activation of B- cells-
• Thymus- dependent : activates B- cells via T- cells
activation, processed by APC
and presented to helper T- cells.
• Thymus- independent : not processed by APC’s.
• Signal Induction and transduction.
ANTIGEN PRESENTATION OF B-CELLS TO ACTIVATED
TH CELLS AND SIGNAL INDUCTION
15. 2. Proliferation and differentiation of B-cells into effector
cells and memory cells.
• Events in dark zone of germinal center:
Centroblast centrocyte low affinity apoptosis
tingible body macrophages
• Events in light zone of germinal center
Centrocyte with high affinity enters light zone and binds
to follicular dendritic cells class switch over
differentiation of centrocytes to plasma and memory cells.
3. Antibody production by plasma cells that counter act
with microbes : neutralization, compliment activation.
16. EFFECTOR FUNCTIONS OF AMI
• Promotes Opsonization
• Transcytosis
• Complemented mediated cytolysis
• Promotes ADCC
