Fundamentals of Immunity

We fight

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

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

Process of Innate immunityPathogen

PAMP- pathogen asso. molecular pattern

Identified by PRR (pattern recog. receptors)

Activate macrophage, dendritic cell, granulocyte, NK cell & complement cascade

Macrophage Derived from monocytes 1st line defense Through hydroxyl radical and NO Attract neutrophils through

prostaglandins, leucotrienes, cytokines

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

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

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

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

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

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

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

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

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

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

Immunity A state of having sufficient biological

defenses to avoid infection or disease Natural (following exposure) or Artif icial

(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)

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

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

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

Immunodeficiency State in which immune system is

compromised or absent Primary (genetic) or

Secondary (malnutrition, aging, steroids, chemotherapy, immunosuppressives, cancer, AIDS)

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