What is Immunology?
Study of physiological mechanisms that humans and other animals use to defend from invading organisms -Bacteria -Fungi -Viruses -Parasites -Toxins
What is Edward Jenner (1790) known for?
Smallpox eradication. Developing Vaccination.
When was smallpox eradicated?
What is Paul Ehrlich (1864-1915) known for?
Worked with Koch. Proposed concept of RECEPTORS (which we now know as antibodies) secreted by immune cells in response to foreign antigens ("magic bullets"). Developed anti-toxin (diphtheria) and haemolysis.
What was elie Metchnikoff (1845-1916) known for?
Discovering phagocytosis (larvae of starfish, similar process to WBCs
What are the stages of Phagocytosis? What is it?
1. Chemotaxis and adherence of microbe to pahgocyte 2. Ingestion of microbe by phagocyte 3. Formation of a phagosome 4. Fusion od the phagosome with a lysosome = Phagolysosome 5. Digestion of microbe by enzymes 6.Formation of residual body containing indigestible material 7. Discharge of waste materials. Allows breaking up of molecules and education of immune cells
What was Sir Frank Macfarlane Burnet (1899-1985) known for?
Clonal selection theory to explain tolerance. Discovery of acquired immunological tolerance.
What is tolerance?
When the immune system ignores a foreign body
What were Benacerraf, Dausset and Snell known for?
Discovered genes regulating immune responses (now known as Major Histocompatibility Antigens MHC or HLA)
What were Milstein, Jerne and Kohler known for?
Monocolonal antibodies. Many new monoclonal drugs: Perception (HER2), Remicade, Avastin. Humanised antibodies now transforming therapy for many diseases (e.g. Rheumatoid Arthritis, Macular Degeneration and Cancer)
What does any immune response involve?
- RECOGNITION of the pathogen - Mounting a REACTION against it to eliminate it
What are the two types of immune response that defend against infection?
-NATURAL/INNATE (non-adaptive) immunity -ACQUIRED/SPECIFIC (adaptive) immunity
What is an antigen?
Any molecule that binds to immunoglobulin or T Cell Receptor and MHC Molecules
What are the genes that regulated immune responses?
MHC - Major Histocompatibility Antigens (called HLA - the Human Leukocyte Antigen - in humans)
What is a pathogen?
A microorganisms that can cause disease
What is an Antibody (Ab)
A Secreted Immunoglobulin (Ig)
Deliberate induction of protective immunity to a pathogen
What are cytokines?
Soluble mediators of inflammation
The process by which a person is made able to resist infection
How many stages can response to infection be divided into?
3 - The first 2 reply on activation of the innate immune system. Innate Immunity (immediate, 0-4hrs) Early Induced Response (early, 4-96hrs) Adaptive Immune Response (late, >96hrs)
What are the stages of the immediate response (0-4hrs) to infection?
Infection Recognition by preformed, non specific effectors Removal of Infectious Agent
What are the stages of the Early (4-96hrs) response to infection?
Infection Recognition of Microbial-associated molecular patterns Inflammation,recruitment and activation of effector cells Removal of Infectious Agent
What are the stages of the Late (>96hrs) response to infection?
Infection Transport of antigen to lymphoid organs Recognition by naive B and T cells Clonal Expansion and differentiation to effector cells Removal of infectious agent
What is adaptive immunity?
This occurs later and results in the clonal expansion of antigen-specific lymphocytes
What are the features of the innate immune response?
Rapid Non-specific First Line of Defence Not Enhanced by repeated exposure
What are the features of the Adaptive Response?
Slow Specific Second Line of Defence Enhanced by Repeated Exposure
What are the Stages of Infection and the protection at each stage?
Adherence to epithelium - Normal flora, Local Chemical Factors, Phagocytes (especially in lung) Local Infection, Penetration of Epithelium - Wound healing induced antimicrobial proteins and peptides, phagocytes and complement destroy invading microorganisms. Local Infection of Tissues - Complement, cytokines, cheekiness, Phagocytes, NK cells Activation of macrophages Dendritic cells migrate to lymph nodes to initiate adaptive immunity Adaptive Immunity - Infection cleared by specific antibody, T-cell dependent macrophage activation and cytotoxic T cells
What are the natural BARRIERS to infection?
Skin, Mucosal epithelial surface of respiratory GI and Urogenital tracts
What are the natural DEFENCES to infection?
Mechanical - Epithelial cells joined by tight junctions (skin,gut, lungs, eyes/nose) Longitudinal flow of air or fluid (skin gut), movement of mucous by cilia (lungs) Chemical - Fatty Acids (skin), Low pH, enzymes e.g. pepsin (gut), Antibacterial peptides (skin,gut,lungs), Salivary Enzymes e.g. lysozyme (Eyes, nose) Microbiological - Normal Flora (skin, gut)
What barriers does Innate Immunity involve?
Non Specific immunity -Anatomic barriers (skin, mucous membranes) -Physiological barriers -Phagocytic Barriers (cells that eat invaders) e.g. dendritic cells and macrophages -Inflammatory barriers
What immune system are the natural barriers and defences a part of?
The innate immune system
What does adaptive immunity involve?
Specific Antigen Specificity Diversity Immunological Memory Self/nonself recognition
How do the two immune responses interact?
Close syngergy between the two, ADAPTIVE greatly improves the efficiency of the INNATE response and the INNATE response setting the scene for activation of the ADAPTIVE response
What cells are involved in the INNATE response
Natural Killer Cells
Macrophage Granulocytes (Basophil,Eosinophil, Neutrophil)
Natural Killer T Cell
gammadelta T cell
What cells are involved in the Adaptive Immune response?
B cell => antibodies T cell => CD4+ T cell and CD8+ T cell gammadelta T cell natural killer T cell
What cells are involved in the innate and adaptive immune response?
Natural Killer T cells Gammadelta T cells
What are the types of ADAPTIVE immunity?
Humoral Immunity : Immunity that is mediated by antibodies, can be transferred by serum to a non-immune recipient
Cell Mediated Immunity : Immune response in which antigen specific T cells dominate
How are the cells of the immune system derived?
Haematopoietic Stem Cell Differentiation
What are NK cells, T and B cells and some dendritic cells derived from?
Common LYMPHOID progenitor cells
What are dendritic cells, monocytes, neurtophils, basophils, eosinophils, mast cells, platelets, erythrocytes all derived from?
Common MYELOID progenitor cell
What stem cells are the cells of the immune system derived from?
Multipotent hemopoietic stem cells
What are macrophages and osteoclasts derived from?
What are Platelets derived from?
What are the components of blood?
Water - (92% weight)
Proteins - Albumins, globulins, fibrinogen, regulatory proteins
Other Solutes - electrolytes, nutrients, rest gases, waste products
BUFFY COAT - Important for clearing bacteria Platelets Leukocytes (Neut,MonoC, Lympho,Eosino,Baso) ERYTHROCYTES 4.3-6.3 million per cubic mm
What are the key cellular components of the INNATE immune system?
Macrophages Dendritic Cells Granulocytes (Mast cells, eosinophils, basophils)
What is a NEUTROPHIL?
Granulocyte (has cytoplasmic granules containing lytic enzymes and bactericidal substances) Polymorhonuclear
SHORT life span (hours
VERY important at 'clearing' bacterial infections INNATE immunity First to arrive upon inflammation though chemotaxis
What are MAST cells
EXPULSION OF PARASITES through GRANULE RELEASE -Histamine, leukotrienes, chemokines, cytokines Also involved in allergic responses Very potent, few in tissue, have a profound effect (^permeability for example)
What are EOSINOPHILS
KILL AB-COATED PARASITES BY DEGRANULATION Involved in allergic inflammation Granulocytes DOUBLE LOBED nucleus Orange granules contain toxic compounds
What are BASOPHILS?
Possibly 'blood mast cells' Kills cells Blue granules containing toxic inflammatory compounds Important in allergic reactions DEGRANULATION
What are LYMPHOCYTES?
Many types important in both humoral and cell-mediated immunity
B-cells = produce ANTIBODIES
T-cells = Naive T cells, Cytotoxic T cells (Tc), Helper T Cells (Th) (CD4+ cells), Regulatory T Cells (Treg) -MEMORY CELLS Can migrate into tissue spaces and lymphoid organs, thereby serving as a bridge between parts of the immune system
Plasma Cell (in tissue): fully differentiated B cells, secretes Ab -Natural Killer Cells (5-10% lymphocytes): Kills tumour cells and virally infected cells, both innate and adaptive, antigen presentation
Describe the action of B Cells
Each B cell expresses one specific type of antigen, the plasma cell will secrete the corresponding antibody which circulate in the serum and diffuse into tissues. Virus is neutralised and eliminated once coated with these antibodies. CLONAL EXPANSION into EFFECTOR CELLS (giving immune response e.g. plasma cells) and MEMORY CELLS.
What are Monocytes?
Circulating precursors of macrophages in blood. PHAGOCYTOSIS and killing of microorganisms = activation of T cells and initiation of the immune response. Phagocytose then Present Antigen (APCs) Circulate for approx 8hrs
What are the types of tissue-specific macrophages?
Peritoneal Macrophages - Gut Kuppfer Cells
Liver Osteoclast - bone development and repair
Microglial cell - brain Histiocytes
What are DENDRITIC CELLS?
Involved in ACTIVATION OF T CELLS and intimate adaptive immunity
Found mainly in Lymphoid tissue Epidermis covered in these
Function as APCs (antigen presenting cells)
MOST POTENT stimulator of T-cell response
Who discovered Dendritic cells?
R Steinman (1943-2011), nobel prize in 2011
What are the major groups of lymph tissues?
PRIMARY Lymph Tissues - where cells originate and mature SECONDARY Lymph Tissues - Where cells reside
What are the PRIMARY lymph tissues?
Thymus - T cell education, get rid of those that react to self Bone Marrow
What are the SECONDARY Lymph Tissues?
Spleen Appendix Lymph Vessels Lymph Nodes (eg. Adenoids, Tonsils, Peyer's Patches in the small intestine)
How does Innate Immunity lead to Acquired Immunity?
Once the antigen is captured, it matures and migrates to a lymphoid organ, activation and clonal expansion of B and T cells occurs. B cells release antibodies CTL helper and regulatory T cells recruit NK cells, Eosinophils and Macrophages.
How are antigens presented to T cells?
Proteins (peptides) from INSIDE the cell are presented by MHC I molecules to Tc cells (VIRUS INFECTED CANCER CELL) Proteins (peptides) from OUTSIDE cells are presented by MHC II to Th cells (APCs) MHC I on almost all cells MHC II on specialised APCs
What do we mean by Self/Non-self?
Self molecules (proteins, DNA, lipids, carbs) are found on our CsTsOs. Our immune system learns to NOT react to these. We have evolved mechanisms to specifically recognise bacterial and viral proteins/lipids and mount an immune response. Once recognised for a second time etc, a STRONGER response is mounted.
Where to T cells originate?
Produced in bone marrow, mature in THYMUS
Where to B cells originate?
Bone marrow, migrate to SPLEEN where they mature.
What are some disorders of the immune system?
What are hypersensitivity reactions?
Over-reaction of adaptive immune response to harmless antigens 4 Types (I-IV) Immune system cannot switch itself off eg.Asthma, Autoimmune disease, Arthus Reaction
What is autoimmunity?
Misdirected adaptive immune response resulting from a loss of self-tolerance 3 Types (II,III,IV) eg. MS, Rheumatoid Arthritis, Diabetes
What are immunodeficiencies?
Components of the immune system are either absent or defective Genetic or acquired aetiology (Malnutritions, Primary IDs)
What is an example of immunosuppression?
Cancer Chemotherapy AIDS
What is on the axis for homeostasis?
Viral Infection => Recovery Bacterial Infection => Tissue Repair (cannot control where toxic granules act, epithelial damage may occur)
What can chronic inflammation cause?
Cancer Transplant Rejection Rheumatoid Arthritis IBD Celiac Disease