Immunology Part 1 LKC Flashcards
(35 cards)
What is the immune system for?
To identify and eliminate harmful “non-self” microorganisms and toxins
To distinguish “self” from non-self proteins
Identify danger signals (inflammation)
Immunopathology
Principles?
Innate vs Adaptive
Broad Specificity vs Exisite Specificity
Minutes vs Days
Generation Times & Evolution?
Bacteria
Virus
Host
Polymorphic variable genes?
Minutes
Hours
Years
Host relies on flexible and rapid immune response
HLA and KIR control immune system, selected for by infectious diseases
Innate vs Acquired Immunity
1) Depends on?
2) Duration? Starting speed?
3) Specificity?
4) Cells involved
5) Soluble Factors Involved
Innate depends on pre-formed cells and molecules
Acquired depends on clonal selection, growth of T/B cells, release of antibodies selected for antigen specificity
Innate is fast (mins)
Acquired is slow (days)
Innate is limited - recognition of danger signals
Acquired is highly specific to foreign proteins ie: antigens
Innate involves Neutrophils, Macrophages, NK cells
Acquired involves T/B lymphocytes, Dendritic cells, Eosinophils, Basophils
Innate involves Acute-phase proteins, cytokines, complement.
Acquired soluble proteins are Antibodies.
Basic Principles of Immune responses and Timescales
Interferon (innate immunity) 1ST
NK cells (innate immunity) 2ND
Cytotoxic T lymphocytes (acquired immunity) END
General Surface Defences
Mech
Chem
Microbiological
Mechanical - Epithelial tight junctions, skin waterproofed by fatty secretions, social conditioning (washing)
Chemical - Fatty acids (skin), enzymes (lysozyme, saliva, sweat and tears) pepsin (gut), low PH (stomach, sweat), Antibacterial peptides
Microbiological - Flora competition for nutrients, production of antibacterial substances
Anatomical Barrier (3)
Skin - keeps out 95% of germs while intact
Mucus membrane in respiratory and GI tract traps microbes
Cilial propulsion on epithelia cleans lungs of invading microbes
Physiological barriers (5)
Low PH Secretion of lysozyme (tears) Interferons Anti-microbial peptides Complement (lyses microorganisms
Cells as barrier
Eos, neutro, baso, NK
Cellular Mediators as barrier
Cytokine, Chemokines, complement, mast cells, secreted products
What is the acute inflammatory response?
Innate response to tissue damage.
Causes rise in body temp : fever response
Increased production of acute-phase proteins in liver.
1) C reactive protein
2) Serum amyloid protein
3) Mannan-binding lectin
C-reactive protein function
Serum amyloid protein function
Mannan-binding lectin function
C-reactive protein and serum amyloid protein bind to molecules on cell wall of some bacteria and fungi. PATTERN RECOGNITION
Mannan-binding lecin binds to mannose sugar molecules not often found on mammal cells
Non-specific, recruiting direct phagocytes (macrophages) to identify and ingest infectious agent
Cells of the Innate Immune System
Granular Leukocytes
NK cells
Identify and kill virus-infected and tumour cells
Recognize HLA molecule of virus-infected cell or tumour and kill them
Macrophages (mononuclear phagocytes)
- Garbage disposal
- Present foreign cells to immune system
Granulocytes
Neutrophils
Polymorphonuclear neutrophil : multi-lobed nucleus
50-70% of circulating WBC
Phagocytic
Cells of the Acquired Immune System
Granulocytes
Eosinophils Bi-lobed nucleus 1-3% of circulating WBC Required for immune response to parasites, helminths and allergic responses
Basophils
less than 1% of circulating WBC
Not Phagocytic - release granules containing histamines, serotonin, prostaglandins
Important in Th2 reponses -kickstarting acquired immune response
What does the innate immune response do? (4)
• Produce interleukins that activate inflammatory pathways (e.g. IL- 1b, IL-18)
• Elicits antiviral defence systems (e.g. type 1 interferon)
• Initiates complement and many other immune products to attempt to destroy the infectious pathogen
• Acts as the immune specific line of defence before the adaptive immune response gets a chance to be engaged
What triggers the innate response? (2)
Triggers of innate response
PAMPs – pathogen-associated molecular patterns
e.g. dsRNA in cytoplasm; bacterial cell wall components.
DAMPs – danger-associated molecular patterns
e.g. monosodium urate, high extracellular [ATP], reactive oxygen species (ROS).
Pattern-recognition receptors
Extracellular danger signals
TLRs – Toll-like receptors
Intracellular danger signals
NLRs – NOD-like receptors
RLRs - RIG-I-like receptors
AIM2
What are some examples of adaptive immunity?
Examples of Adaptive Immunity
• T cells- such as CD8+, CD4+, CD3 and their products (e.g. cytokines) - cellular immunity
• B cells- such as Plasma cells, and memory B cells and their products (e.g. antibodies) -humoral immunity, CD19, Surface immunoglobulin class II MHC
• Antigen presenting cells (e.g. dendritic cells and macrophages) –these actually bridge the innate and adaptive immune response
Note: The innate immune system: buys time while the acquired immune system is mobilized, and helps to stimulates the acquired immune response
What are antigens?
Antigens are glycoprotein molecules which react with antibodies or T cells. However not all antigens can induce an immune response in the host: those that can are termed immunogens
What are antibodies?
Antibody molecules can be found in the blood stream and the body fluids and bind specifically to particular molecules termed antigens. They are the acquired component of the humoral immune response.The most basic antibody molecule is bivalent- with two antigen binding sites.
Immunoglobins (5)
IgG
- 75% of our serum
- Crosses placenta, therefore important in protecting newborns
- Long serum hal-life
- Part of secondary immune response
- Bivalent- two identical antigen binding sites
IgM
- 10% of total serum Ig
- Complex of 5 linked bivalent monomeric antibodies, therefore 10 identical binding sites- multivalent
- Star-like shape
- Important in primary immune response
- Slightly lower affinity to antigens compared to IgG, which is compensated for by number of binding sites
IgA
- 2 basic monomers; dimer with secretory piece
- Found in body secretions, e.g. mucus membranes in GI tract
- Contains a secretory component which protects it from digestive enzymes
IgE
- Involved in allergic response and the response to helminths
- Binds to basophils and mast cells
- Triggers release of histamines
IgD
- Complete function not known
What are chemokines?
• Small bioactive proteins that are secreted by cells that act to recruit or control the migration of other cells
• Four broad classes due to structure – CXC (E.g.
– CCR –C
– CX3C
What is the basis of specificity of antigen?
Antibody’s binding site is complementary to the EPIPTOPE (region approx 6 amino acids long) on the antigen
How does an antibody kill a virus? (4)
- Neutralization : Binds to the virus and prevents attachment to the cell
- Opsonisation: virus-antibody complex is recognised and phagocytosed by macrophage
- Complement- mediated lysis of enveloped viruses: cascade of enzymes in the blood which leads to the destruction of cell membranes, and the destruction of the viral envelope
- Antibody-dependant cell-mediated cytotoxicity (ADCC) mediated by NK-like cells (HLA molecule)
Cells of the acquired immune system?
Lymphocyte
- Agranular leukocytes
- 20-40% of the circulating WBC
- 99% of the cells in lymphatic circulation
T (thymus-derived) cells
- Helper T cells: recognize antigen, help B cells to make antibodies and T cells to kill
- Cytotoxic T cells: poisonous to cells,kill cells infected by viruses and intracellular bacteria
B (bone marrow-derived) cells
- Make antibodies
- Have insoluble antigen-binding receptor on its surface. In fact have multiple clones of this receptor;
monoclonal antibodies
NK (natural killer) cells
Each subset has distinct cell-surface molecules, e.g. CD4 on helper T-cell which is the receptor for HIV molecules
Lymphocyte precursors are produced in the haematopoietic tissue in the bone marrow
T cells then transported to the thymus, where they undergo THYMAL EDUCATION, here 95-99% get destroyed as they have the potential to recognise host cells
