1. Fundamentals of Immunity
We fight

2. Definition
 Immune system is a system of
biological structures and processes
within an organism that protect from
and help fight disease
 Includes liver, spleen, LN, leucocytes,
complement system, MHC/HLA etc.
 Immune response, unlike inflammatory
response is specific and has memory

3. Innate immune system
 Present in all organisms
 Non-specific immune response
 Immediate maximal response
 Cell-mediated and humoral components
 No immunological memory

4. Process of Innate immunity
Pathogen
PAMP- pathogen asso. molecular pattern
Identified by PRR (pattern recog. receptors)
Activate macrophage, dendritic cell,
granulocyte, NK cell & complement cascade

5. Macrophage
 Derived from monocytes
 1st
line defense
 Through hydroxyl radical and NO
 Attract neutrophils through
prostaglandins, leucotrienes, cytokines

6. Dendritic cell
 Phagocytes in tissues
 Found in skin, nose, lungs, stomach
and intestines
 Act as Ag presenting cell, thus linking
innate and adaptive immune systems

7. NK cells
 5-10% of peripheral blood lymphocytes
 Has receptor for Fc portion of IgG that
mediates ADCC
 NK cell activity may be non-Ab
mediated also to kill malignant cells
 Do not kill cells with MHC I expression,
thus prevent normal host-cell damage

8. Granulocytes
 Neutrophil- express Fc receptors for IgG &
activated complement components
 Eosinophil- express receptor for IgG
 Basophil- express receptor for IgE & activated
complement components
 Release enzymes, superoxide radical,
peptides and histamine that cause
inflammation and are nonspecific amplifiers &
effectors of immune response

9. Complement system
 A cascading series of plasma enzymes
synthesized in liver that can cause cell lysis &
complement immune response
 Activation pathways
 Classical- Ag-Ab complex, rapid
 Mannose binding lectin pathway
 Alternative- recog. bact./virus/tumor cells,
slow & inefficient

10. Complement components
 C3a, C5a- histamine release
 C5a- chemo-attractant for monocytes
and neutrophils
 C3b- activates terminal components,
promotes immune-complex binding &
phagocytosis by mono./neutrophils
 C5b-9- membrane attack complex,
brings about osmotic lysis of cell

11. Adaptive immune response
 Found only in vertebrates
 Pathogen and antigen specific
response
 Lag time between exposure and
maximal response
 Cell-mediated and humoral components
 Exposure leads to immunological
memory

12. A.I.R. mediators
 B-cell- mature in bone-marrow, recognize
natural unprocessed antigens causing
humoral antibody mediated response
 T-cell- mature in thymus, recognize
processed antigen (Ag + HLA), causing cell
mediated response
 Ag presenting cell- monocyte/macrophage,
dendritic cell, B lymphocyte

13. B-cell
 Develop in bone marrow
 Found in follicles of lymph nodes
 Precursor of Ab secreting plasma cells
 Express surface Ig
 Activation by Ag and T-helper lympho.
 Also act as Ag presenting cell

14. T cell- helper
 CD4
 Found in paracortex of LN
 Responsible for initial cell mediated response
 Recognize HLA class II Ag- DP, DQ, DR
 Secrete interleukins and interferons
 Cause antiviral, anti mycobacterial,
antiinflammatory, immunosuppressive
response
 Lead to memory

15. T cell- killer/cytotoxic
 CD8
 Found in paracortex of LN
 Responsible for final cell mediated
response
 Recognise HLA class I Ag- A, B, C
 Act against virus, intracellular
pathogens & malignant cells
 Lead to memory

16. Immunity
 A state of having sufficient biological
defenses to avoid infection or disease
 Natural (following exposure) or Artificial
(following vaccination/IVIG infusion)
 Passive (acquired through transfer of Ab or
activated T-cells from an immune host, short
lived e.g. placental/colostrum transfer) or
Active (induced in
the host itself by Ag, long lasting)

17. Immunological tolerance
 Ability of an individual to ignore self, while
reacting to non-self
 Theories-
 Clonal deletion- during development of immune system
 Clonal anergy- self-reactive lymphoid cells become inactivated
& cannot amplify immune response
 Idiotype network- presence of Abs. capable of neutralising
self-reactive Abs.
 Clonal ignorance- host immune response ignores self Ags.
 Regulatory T-cell- regulatory T-cell prevent, downregulate or
limit autoimmune response

18. Autoimmunity
 Failure of an organism to recognize its
own constituents as self
 Allowing an immune response against
its own cells and tissues
 Leading to an autoimmune disease
 e.g. Type 1 DM, SLE, RA, ITP, AIHA,
Graves’ disease, Pemphigus

19. Pathogenesis of autoimmunity
 T-cell bypass- super Ag produced by some
infections can initiate polyclonal B-cell
activation
 T-cell & B-cell discordance in response to
different Ags.
 Self-perpetuating autoreactive B-cell
 Molecular mimicry- an exogenous Ag sharing
structural similarities with host Ag

20. Immunodeficiency
 State in which immune system is
compromised or absent
 Primary (genetic) or
Secondary (malnutrition, aging, steroids,
chemotherapy, immunosuppressives, cancer, AIDS)

21. Primary immunodeficiency
 Combined T & B cell- SCID
 Ab deficiency- CVID, Bruton’s agammaglobulinemia-
recurrent infection with S. pneumo./H. influ.
 Syndromes- Wiskott-Aldrich, DiGeorge
 Immune dysregulation- Chediak-Higashi
 Phagocyte disorder- Cyclic neutropenia, Chronic
granulomatous disease- recurrent
Staph. skin infection
 IIR deficiency- WHIM syndrome
 Autoinflammatory disorder- FMF
 Complement deficiencies predispose to Neisseria
infection or cause autoimmune disease