Week 9 - Immunity Flashcards
What are the primary lymphoid organs?
Bone marrow
Thymus
What are the anti-microbial secreted immunity mediators?
Antibodies
Defensins
Interferons
Lytic enzymes
Cytotoxins
What are the regulatory / inflammatory secreted immunity mediators?
Cytokines
Chemokines
Prostaglandins
Histamine
What are the properties of innate immunity?
Quick activation
Same upon repeated exposure to same microbe
Moderate efficiency
General response to microbes
Recognition of PAMPs (pathogen-associated molecular patterns)
Recognition by PRRs (pattern recognition receptors)
What are the properties of acquired immunity?
Slower activation
Improvement on repeated exposure to same microbe
High efficiency
Specific response to individual microbes
Recognition of antigens specific to each microbe type
Recognition by antigen-specific receptors clonally expressed by lymphocytes
What is the primary immune response?
Epithelial barrier
Immediate local response / innate response (complement proteins and macrophages)
Early induced response / innate / inflammatory response (inflammatory mediators from complement, macrophages, mast cells –> attract leucocytes and serum proteins)
Later adaptive response (antigens carried to lymphoid tissue by dendritic cells –> T / B lymphocyte activation and Ab production –> recirculation to infection site)
What is immunopathology?
Diseases involving defects in the immune system (immunodeficiency, allergy, autoimmunity, transplant rejection, lymphoproliferative diseases)
What are the properties of B lymphocyte antigen recognition?
Antigen recognition receptors = membrane bound immunoglobulins
Surface immunoglobulins = surface receptors
Secreted immunoglobulins = antibodies
All receptors are identical on 1 cell
Interaction of antigen and receptor = B cell activation / proliferation
Further differentiation to form plasma cells
What happens during clonal selection?
Clone with most specific surface immunoglobulins = have primary response then secondary response to the infection –> less specific don’t undergo response to infection
What are the properties of blood?
A tissue
8% body mass
45% RBCs
1% WBCs and platelets
55% is plasma –> albumins = transport, colloidal osmotic pressure – globulins = transport, clotting, precursors to hormones, defence – fibrinogen = clotting
Serum = coagulated plasma
What are the properties of blood cells?
Discoid
No nucleus
Has haemoglobin for O2 / CO2 transport
120 day lifespan
Foetus and neonatal production = liver and spleen
Neonatal, child and adult production = bone marrow
What are the 5 leucocyte types and their proeprties?
Neutrophils = microorganism phagocytosis
Eosinophils = parasite killing and inflammation
Basophils = histamine release in hypersensitivity reactions
Monocytes = phagocytic, leave blood and become macrophages
Lymphocytes = produce antibodies
What are the types of phagocytes and immunocytes?
Granulocytes
Monocytes
Lymphocytes
How is white blood cell production controlled?
Colony-stimulating factors
CSFs stimulated by infection
Recombinant CSFs = improve reduced WBC count after anticancer drugs
Interleukins
What are the different blood groups and their properties?
Determined by RBC antigens
ABO and Rhesus = clinically important ones
A = A antigens, b-antibodies
B = B antigens, a-antibodies
AB = AB antigens
O = no A or B antigens, has a and b antibodies
O Rh -ve = universal emergency donor
What are the properties of blood counts?
Cells per volume –> machine or manually calculated
Haematocrit / packed cell volume –> centrifuge blood and find RBC % (male = 40-52%, females = 36-48%)
Haemoglobin –> amount per 1 Litre (males = 135-175 g/L, females = 115-155 g/L)
Identify anaemias
Mean corpuscular volume –> volume of individual RBCs –> identifies microcytic, macrocytic anaemia and alcohol abuse
What is Hb/RBC and Hb/PCV?
Hb/RBC = mean corpuscular Hb – reduced with iron deficiency or small cell size
Hb/PCV = mean corpuscular Hb conc. – reduced when large cells with impaired haem production
What are Rhesus D antigens required for?
+ve or -ve
Required in pregnancy –> new-born haemolytic disease
Prevent with Anti-D immunisation – Anti-D immunoglobulin
Give to mother after 1st child delivery
What are the components of blood and their functions?
RBCs:
Oxygen transport
WBCs:
Immune defence
Platelets:
Clotting
Plasma
What are not detected in blood?
Plasma calles
Macrophages
Mast cells
What are the properties of mast cells?
Recruit circulating leukocytes. Widening of vessels –> slower flow, induce arrestins –> inflammation, swelling
In most slides, mast cells have lost their granules due to the preparation Toluidine stained resin sections
What are the properties of macrophages?
Engulf foreign substances and cells and digest their contents.
Large cells, nucleus generally light, oval or even dented, often with nucleolus
What are the properties of plasma cells?
“antibody factories” differentiated from B-lymphocytes
Characteristic round nucleus with heterochromatin clumps around the periphery and in the middle. The nucleus is often off centre.
What are the properties of leukocytes?
Attracted to infected site from bloodstream –> swelling = caused by loosening of epithelial junctions for cell transit
What are secreted immune mediators?
Granulocytes, macrophages, natural killer cells, mast cells
Limited specificity
+ destructive power
Where are B and T lymphocytes generated?
In bone marrow
What happens during clonal selection of T cells?
Epitope binds to T cell receptor
T cell multiplies rapidly
Identical progeny formed
What happens during B cell differentiation?
Antigen binds with epitope to B cell receptor
Clonal amplification
Differentiate into plasma cells
Shed receptors, forming antibodies
What happens at the secondary lymphoid system?
Matching venues (lymph follicles, tonsils, lymph nodes, spleen):
where antigens and lymphocytes are matched
What are matching venues?
Appear as aggregates of many lymphocytes
Site of antigen presentation, T and B cell activation and expansion
Reticular fibres allow lymphocytes and APCs to circulate around them
Lymphocytes exit/enter via blood vessels with broadened epithelia
What is a lymph nodule?
What are tonsils?
What are lymph nodes?
Just underneath epithelia, no distinct connective tissue capsule –> common in airways and digestive tract
Aggregate of lymph follicles in partial collagen capsule
Encapsulated aggregates of follicles with lymph percolating through them
How are subclavian veins formes?
Leaky capillary system around lymph nodes
Liquid is pressed into interstitial tissue
Liquid is collected in lymph capillaries
These congregate into lymph vessels
Subclavian veins form with lymph nodes in-between
What is a complement?
Collection of proteins found in tissue fluids and circulation
Act as activation enzymes, immune defence molecules, control proteins
Infection and immune activation activate complement proteins, occurring as chain reaction
Activation steps = involve enzymes splitting complement proteins
What does Fc region of antibody bind to and when?
C1q, only is it is bound to an antigen too
What happens during the MBL pathway?
MBL = interacts with microbial surface instead of antibody –> activates MASP-1/2
Generates C3 convertase
What happens during the alternative pathway?
Uses compliment proteins to form C3 convertase
How does the membrane attack complex work?
Destroys microbe by punching holes in its membrane
What are the properties of extracellular digestion?
For parasites as they vary in size
Attaches to antibodies
Releases digestive vesicles instead of phagocytosis
What happens during mast cell mediator release?
Soak up IgE on surface
Gain antigenic specificity of antigen
Cross-linking = IgE binds to both receptors
Activates mast cell
C3a and C5a compliment proteins also activate mast cell
Mediators released, causing inflammation
What happens during the acute phase response to infection / systematic inflammatory response?
Inducing cytokines – act on hypothalamus, liver and bone marrow
Fever
Leucocytosis from bone marrow
Acute phase proteins released from liver
What is bacterial taxonomy important for?
Handling information
Learning
Communication
Identification
Evolution
What are the ways bacteria is phenotypically classified?
- Morphology (Growth on agar medium: shape, margin, elevation, size, texture, appearance, pigmentation, optical density) (Single cells: Shape – rod, club, coccus, curved, spirillum, spirochaete, size, staining characteristics – Gram stain = true bacteria, Acid fast stain = mycobacteria, arrangement) Spores + capsules
- Bio-typing
- Serotyping
- Antibiogram patterns
- Phage typing
What are the ways bacteria is genotypically claffisied?
DNA hybridisation
Nucleic acid sequence analysis
Chromosomal DNA fragment analysis
Ribotyping
What are the properties of gram stain on bacteria?
Differentiates bacteria on cell wall structure
First test for bacterial infection diagnosis
Gram positive = thick cell wall
Gram negative = thin cell wall
What are the bacteria cell wall functions?
Maintain cell rigidity and structure
Maintains osmolarity (prevents osmotic lysis)
Survival
Cell division
How is bacteria cell wall synthesised?
Synthesis of peptidoglycan precursor in cell
Exported across cell membrane
Enzymic action creates site in existing wall
New nucleotide is incorporated minus terminal D-ala
Cell grows
What are the properties of a mycobacterium cell wall?
Mycolic acid waxy coat
Poor gram stain
Acid fast
What are the properties of a mycoplasma cell wall?
No cell-wall
Steroids in cell membrane
What are the properties of bacteria cell membrane?
Hydrophobic lipid bilayer
No steroids
Gram + and – bacteria
Ion transport and energy production
Mesosomes for cell division
What are the growth characteristice for bacteria?
O2/CO2
Temp
Water
pH
Light
Osmolarity
What are bacteria nutritional requirements?
Carbon source
Nitrogen source
Inorganic salts
Organic compounds
What were the effects of groups on weight loss, smoking cessation and alcohol use?
Mostly female, significant weight change after 12 months in group than individual
5 weekly sessions, led by group members, self-help and nicotine replacement therapy, double rate of quitting in group than alone
Inconclusive
What are the types of social support?
Perceived support, received support and structural support (integration into social network)
Emotional
Tangible (financial)
Informational
Companionship
What is loneliness?
What is social isolation?
What is solitude?
Difference in preferred and actual level of social contact
Having minimal social contact
Voluntary distance from social network
What is test sensitivity?
What is test specificity?
Proportion of those with diseases which it correctly identifies
Proportion of those without disease which it correctly identifies
What is positive predictive value?
What is negative predictive value?
Probability a subject has disease given they have positive result –> determined by prevalence and sensitivity and specificity
Probability a subject doesn’t have disease given they have negative result
What is a diagnostic test?
What is a screening test?
What is a prognostic test?
Confirm or exclude presence of a disease
Asses risk of disease in asymptomatic person to determine need for further diagnostic testing
Asses risk of future disease and need for preventative measures
What is likelihood ratio?
Likelihood a positive test would be expected in a patient with disease compared to likelihood in patient without disease
What are the 3 components of attitude?
Affective component - emotions
Behavioural component - actions
Cognitive component - thoughts / beliefs
What must attitudes be to be consistent?
Stable
Important
Certain
Consistent between cognition and affect
Easily accessed
Formed through direct experience
What is stigma?
What is cognitive dissonance?
Cluster of negative attitudes and beliefs, motivating general public to fear, reject, avoid and discriminate against a particular group based on identifying feature
When thoughts / beliefs / feelings don’t match behaviour or action - can cause attitude change or avoidance
What is discredited and discreditable stigma?
Visible stigma
Invisible stigma
What is B cell antigen receptor made of?
What is T cell antigen receptor made of?
Surface immunoglobulin
2 polypeptide chains (TCR ‘alpha’ and ‘beta’ chains)
Both are anchored in surface membrane
Each composed of 2 immunoglobulin-like domains
How many antigen combining sites do B and T cells have?
What is the role of T helper cells?
What is the role of T cytotoxic cells?
- Help other immune cells fulfill their function
- Activate B cells
- Stimulate phagocytotic activity of macrophages
What are HLA proteins and their role?
- Human antigen-binding proteins
- Associate with proteins that hold peptides on APC surface
What are the properties of HLA class 1 proteins?
- Have large ‘alpha’ chain non-covalently associated with ‘beta’2-microglobulin polypeptide
- ‘alpha’ domains of ‘alpha’ chain form cleft/groove on surface of protein
- Groove formed distal to surface membrane
- Present antigen peptides to Tc cells
- Interact with CD8 on Tc cells
What are the properties of HLA class 2 proteins?
- 2 polypeptide chains (class ll ‘alpha’ and ‘beta’ chains)
- Have immunoglobulin-like domains Proximal to surface membrane
- Distal domains form peptide binding cleft
- Present proteins to Th cells
- Interacts with CD4
What is the purpose of CD8-Class 1 and CD4-Class 2 interactions?
- Strengthen overall APC and T cell binding
- Provide additional activation signals
- Both members of Ig superfamily
What happens during processing of antigens for presentation by HLA class 1 proteins?
- Degradation of endogenous protein antigens in cytoplasm
- Degraded in proteasome enzyme complex
- Some peptides transferred for endiplasmic reticulum vie peptide transporter proteins
- Some associate with new HLA class 1 proteins
- New compelxes translated to cell surface for recognition by Tc cells expressing CD8
What happens during the process of antigen processing for presentation by HLA class 2 proteins?
- Internalisation of exogenous protein antigen into vesicle by endocytosis
- Antigen degraded by enzymes entering vesicle
- New HLA class 2 in endoplasmic reticulum associate with invariant chain and go to vesicle
- Invariant chain is degraded and antigen associate with HLA class 2 protein
- HLA class 2 transported to cell surface for recognition by Th cells expressing CD4
What are the differences between HLA class 1 and 2 proteins in the body?
- HLA class 1 expressed by most cells in body
- HLA 2 expression restricted to immune system cells
What are the properties of DCs (dendritic cells)?
- Primary stimulators of naïve resting T cells
- Capture antigens and transport them to lymphoid tissue
- Can activate both Tc and Th cells as their peptides bind to both HLA class 1 and 2 molecules
- Activated when microbial molecules bind to them
- Produce cytokines which activate T cells, once activated
