10) Blood And Immunity Flashcards
(120 cards)
1
Q
What is a primary immune response
A
The first exposure to a microbe that then induces immunological memory
2
Q
What is a secondary immune response
A
Re exposure to the same microbe that leads to adaptive immunity
3
Q
What are lymphocytes
A
White blood cells - can be divided into B cells and T cells
4
Q
5 infectious agents
A
Viruses Bacteria Fungi Protozoa Worms
5
Q
What are neutrophils, eosinophils and basophils
A
Circulating cells that can be categorised as granulocytes (contain granules in their cytoplasm)
6
Q
What are granulocytes
A
Any group of WBCs that when stained with romanowsky stains are seen to contain granules on their cytoplasm
Can be sub classified on the basis of the colour of their stained granules into neutrophils, eosinophils and basophils
7
Q
What is the difference between secreted mediators of immunity that are anti-microbial compared to regulatory / inflammatory
A
Anti microbial have direct, effective effects- destroy and eliminate microbes from the body
Regulatory - control occurrence and size of immune responses
8
Q
Define recognition and defence
A
Recognition- interaction with microbes and their components
Defence- elimination of microbes and their products
9
Q
What is adaptive immunity
A
The ability of the immune system to adapt to having made a response to a particular infecting microbe (if there’s re exposure to that microbe, a better and more efficient response can be generated)
- slowly activated
- improves on repeated exposure to the same microbe
- high efficiency
- specific response tailored to individual microbes
- recognition of antigens specific to each type of microbe
- recognition by antigen-specific receptors clonally expressed by lymphocytes
10
Q
What is innate immunity
A
Quickly activated
- remains the same on repeated exposure to the same microbe
- moderate efficiency
- unlikely to give sufficient protection against a virulent microbe
11
Q
What are pathogen associated molecular patterns (PAMPs)
A
Chemical structures of the microbes / pathogens which distinguish them from anything that is naturally part of our own bodies
Eg double stranded RNA found in viruses as humans only make single stranded
12
Q
Outline the stages of a primary immune response
A
1) epithelial barrier
2) immediate local response (innate) - complement proteins, macrophages
3) early induced response (innate / inflammatory)
Inflammatory mediators from complement, macrophages, mast cells- attract leucocytes and serum proteins (more complement)
4) later adaptive response - antigen carriage by dendritic cells to lymphoid tissues activation of specific T and B lymphocytes and Ab production recirculation to site of infection
13
Q
What is severe combined immunodeficiency (SCID)
A
Primary immunodeficiency
Involves genetic defects in lymphocytes
Results in not being able to generate T or B lymphocytes
Treatment: Bone marrow transplant to be able to produce stem cells
14
Q
Name 5 types of immunopathological conditions
A
Immunodeficiency Allergy Autoimmunity Transplant rejection Lymphoproliferative diseases
15
Q
What are the cellular constituents of the immune system
A
WBC (leucocytes), cells in specialised tissues and cells scattered throughout most tissues of the body.
Can be categorised according to their developmental origin from stem cells in bone marrow (myeloid / lymphoid) or their morphology
16
Q
5 characteristics of blood
A
- cells suspended in a fluid medium called plasma (cells 35%, plasma 55%)
- vehicle to transport gases, nutrients, cells, hormones, antibodies and metabolites around the body (5-6L)
- has a role in maintaining body temp
- formed in bone marrow (haematopoiesis)
Fluid containing proteins (8%), salts (1%) and lipid (0.5%)
17
Q
Cellular components of blood
A
Red blood cells - erythrocytes (>98%)- biconcave disc, anuclear, no organelles
- WBC - leucocytes (<2%)
- platelets (thrombocytes) (0.002%)- small anuclear fragments of megakaryocyte cells in bone marrow
18
Q
What types of WBC are granular and what are agranular
A
Granular: neutrophils (40-75%), eosinophil (5%), basophil (0.5%)
Agranular: lymphocyte (20-50%), monocyte (1-5%)
19
Q
Functions of RBC, platelets, plasma, WBCs
A
RBC- transport oxygen from lungs to peripheral tissue
Platelets (thrombocytes)- adhere to defects in blood vessels and assist in clotting mechanism
Plasma- transport gases, nutrients, cells, hormones, antibodies and metabolites around the body
WBCs- main function is outside the vessels. Destroy infecting organisms and remove dead and damaged tissue
20
Q
Functions of different types of WBCs
A
Neutrophil - leave circulatory system in response to tissue damage. Remove damaged tissue and kill and phagocytose invading organisms. Increased in bacterial infection and inflammation
Eosinophil- elevated in allergic reactions and in parasitic infection
Basophil- phagocytosis, produce heparin and histamine
Lymphocyte- immunologic response (antibodies) increased in viral infections
Monocyte- phagocytosis. Rarely elevated
21
Q
What do blood tests tell us
A
- important indicator of disease
- can indicate disease of the blood / marrow / circulatory system/ heart
- contains molecules in the process of being transported - these can be analysed to give info on disease processes in other organs
- abnormal numbers of cells give info about disease processes
- easy to obtain
22
Q
How is a blood analysis done
A
Full blood count: sample of blood sent to laboratory. RBC, wbc and platelets are counted
Tests for, diagnoses and monitors many different conditions
23
Q
What things do you find from a blood analysis
A
- fraction of blood composed of RBCs: haematocrit
- erythrocyte sedimentation rate: rate at which the red blood cells settle to the bottom of the test tube
- total Hb in blood
- mean cell Hb (from Hb and RBC)
- mean cell volume (average volume of RBC)
- mean cell Hb conc (average conc of Hb in a given volume of packed RBCs)
24
Q
What may abnormal blood analysis results tell you
A
- high numbers of RBCs or a high hematocrit - dehydration
Low numbers of RBCs or low hematocrit- anemia
Low Hb- anemia, blood loss
Low WBC (leukopaenia) - Bone marrow failure
High WBC (leukocytosis)- infection and inflammation, leukaemia
25
What enzyme is elevated in blood when cardiac muscle is damaged
Cardiac troponin- T and creative kinase (MB isoform)
26
What enzyme is elevated in the blood when hepatocyte is damaged
Alanine transaminase
| Aspartate transaminase
27
What enzyme is elevated in the blood when striated muscle is damaged
Creating kinase
28
What enzyme is elevated in the blood when exocrine pancreas is damaged
Amylase
29
What are the acute phase plasma proteins in the blood
Fibrinogen
C reactive protein
Serum amyloid A
30
If there is increased conc of acute phase plasma proteins in the blood what are the systematic effects on inflammation
- act on the brain to increase temp (fever), reduce appetite and increase fatigue
- act on the bone marrow to increase the production of neutrophils (neutrophilia particularly in bacterial infection)
- mediated by cytokines especially TNFa, IL-1(SAA) and IL-6(CRP and fibrinogen)
31
How does formation of blood cells (haematopoiesis) occur
(Initially in yolk sac then embryonic liver and spleen)
- bone marrow at 20 weeks gestation
By birth it only occurs in BM
In adults only occurs in proximal long bones, ribs, sternum, pelvis and vertebrae
32
What conditions does haematopoiesis require
Proliferation and differentiation to produce a variety of mature blood cells with specialised functions from progenitor cells
33
3 characteristics of haematopoietic stem cells
1) there are very few of them
2) they can self renew
3) the majority of progeny are not stem cells but have started the process of differentiation
34
What is differentiation in terms of haematopoiesis
The stepwise changes that occur over successive generations of cells that result in specialised function
35
What are the 2 lineages of cells
Myeloid and lymphoid
36
What are myeloid cells
* erythroid series (RBC)
* granulocytes series (neutrophils, monocytes / macrophages, eosinophils, basophils)
* megakaryocytes (platelets)
37
What are lymphoid cells
B and T lymphocytes and related cells
38
What is leukaemia
- malignancy of bone marrow
- malignancies of immature haematopoietic cells that are present in the blood and bone marrow (increased number of circulating leucocytes is usually seen)
- the malignant cells can either be myeloid or lymphoid
39
What are acute leukaemias (characteristics)
- increased immature cells (blasts) in marrow
- short survival if untreated
- clinical features of bone marrow failure because the normal production of cells is crowded out by the rapidly growing malignant cells
40
Clinical features of acute leukaemias
- reduced production of red cells : breathless, dizzy, fatigued, pale
- reduced production of mature myeloid cells: susceptible to bacterial or fungal infection
- low platelet count : bleeding in skin, gums, nose, gut
41
Describe the 5 cardinal symptoms associated with inflammation and tissue damage
```
Pain
Redness
Heat
Swelling
Loss of function
```
42
Blood flow through the tissue in microcirculation in acute inflammatory vasodilation depends on..?
1) systemic arterial pressure (function of CO and total peripheral resistance)
2) local vascular resistance (arteriolar tone)
43
Why do capillaries have a mono layer of endothelial cells
They passively respond to hydrostatic pressure
44
What factors can influence vascular resistance (arteriolar tone)
I) neuronal constrictor and dilator influences eg noradrenaline and sensory nerves
II) endocrine and paracrine hormones (angiotensin II and PGs)
III) pO2 and pCO2
45
What is bradykinin
Direct vasodilation and release of endothelial prostaglandins. Bk also stimulates nociceptors (sensitised by PGs)
46
What are the agents that increase venular permeability and how do they do it
Venular permeability is increased by contract pore proteins elevating Ca2+
1) histamine - H1 receptors
2) bradykinin
3) leukotriene C4 and D4 and platelet activating factor (PAF)
47
What are the agents that decrease venular permeability and how do they do it
Venular permeability is decreased by relaxing pore proteins by cyclic AMP
1) B2-adrenoreceptor agonists - terbutaline, salbutamol
2) PGI2
48
What is a triple response in the skin
1) initial ‘flush’ in the area of damage. Release of histamine from mast cells and immediate vasodilatation
2) ‘flare’- extensive vasodilatation in unmanaged area surrounding ‘flush’ (redness) orthodromic activation of sensory nerves (pain and itching) and antidromic activation of branches causes release of substance P, CGRP and VIP
3) ‘wheal’ - oedema (swelling) in damaged area. Later event associated with the ‘flush’- direct damage to the endothelium. Activation of complement and / or mediator of vascular permeability leads to protein extravasation
49
What makes up the primary lymphoid tissue
Bone marrow - B cell maturation
| Thymus - T cell maturation
50
What is involved in the secondary lymphoid tissue
- lymph nodes
- spleen
- mucosa associated lymphoid tissue (MALT) eg tonsils, adenoids, peyer’s patches and diffuse cells in respiratory, genitourinary and gastrointestinal systems
51
What is lymph
Interstitial fluid from capillary beds, not picked up by venules. 20% of interstitial fluid ends up as lymph (is returned to the circulatory system via lymphatic vessels) §§
52
What are lymphatics
Open ended tubes that carry lymph back to the venous circulation (subclavian veins) via the thoracic duct or right lymphatic duct
53
What is lymphoedema
A swelling caused by blocked lymph vessels / nodes which prevents drainage - can be a side effect of radiotherapy
54
What are dendritic cells / macrophages
Antigen presenting cells lining exposed surfaces and resident within tissues.
55
What are lymph nodes
Cortex (outer) and medulla (inner) supported by a reticular network and surrounded by connective tissue capsule
56
How does lymph come into the lymph nodes
Enters via afferent lymphatics into a network of sinuses (subcapsular, cortical and medullary) which ultimately drain into efferent lymphatics
-macrophages and dendritic cells enter the node via lymphatics
57
Why do lymphocytes travel constantly between lymph nodes and other secondary lymph organs
In search of a matching antigen
58
How do lymphocytes travel
They can (and do) travel in the lymph vessels but majority (90%) travel in the bloodstream
59
How do lymphocytes travel through the lymph nodes
They enter the lymph nodes at the sites of high endothelial venules, normally located in the paracortex (which have cubodial endothelia)
Most leave via the efferent lymph vessels from where they will eventually enter the bloodstream again
60
What happens when a macrophage or dendritic cell ingests a microbe
It is activated and travels in lymph to the closest node to present protein fragments
61
What does the lighter staining of the germinal centre indicate
Secondary follicles in the cortex
Represents areas of B cell maturation, in which some of the activated B cells die off. The others differentiate into plasma or memory cells
62
What do larger pale nuclei in the cortex of a lymph node represent
Follicular dendritic cells which hold and present antigens during this maturation process. Germinal centres indicate an active B cell response
63
4 times when lymph nodes would be enlarged
- infection ( working hard)
- when they are infected eg with TB
- tumour of the lymphoid system (lymphoma)
- when a tumour metastasises to nearby lymph nodes eg from breast or colon tumours
64
Lymphoma
Malignancies of mature lymphoid cells
The malignant cells predominantly proliferate in the lymph nodes and spleen
Lymphocytes in bone marrow and blood are sometimes involved
65
Role of the Spleen
- does to blood what a lymph node does for lymph
- filters circulating blood through sinusoids to remove effete RBCs and platelets
- phagocytosis blood borne microorganisms
- mounts an immune response to antigens in the blood
- therefore following splenectomy (trauma / tumour) a patient will exhibit: infection, increased no of deformed RBCs and platelets
66
Characteristics of the spleen
- comprised of a collagenous capsule surrounding a reticulin network
- the reticulin network supports many sinusoids and lymphoid aggregates
- blood enters and leaves at the hilum via the splenic artery and vein
- blood entering the spleen ends up in sheathed capillaries (lined with macrophages)
- bad cells cant squeeze through the gaps into the venous sinuses and are phagocytosed by the macrophages. Good cells pass into the sinuses which drain into veins
67
What is mucosa associated lymphoid tissue (MALT)
- single cells or aggregates of lymphocytes
- lymph follicles or nodules: just underneath epithelia. No distinct connective tissue capsule. Frequent in airways and the digestive tract
- principle sites of antigen presentation and T and B cell activation and expansion
- kept in shape by a network of fine reticular fibres that allow lymphocytes and APCs to circulate around them
- have blood vessels with broadened epithelia for entry / exit of travelling lymphocytes
68
What is the epitope of an antigen
The precise region that physically reacts with the antigen combining site
69
Define immunoglobulin
One of a group of structurally related proteins that act as antibodies
70
What are pattern recognition receptors
Expressed by leucocytes
| Germline-encoded host sensors that detect molecules typical for the pathogens
71
What are toll like receptors
They are pattern recognition receptors (PRRs) but expressed by macrophages, dendritic cells and other cell types - react with microbial PAMPs to generate immune activity
72
Define antigen
Any molecules that is recognised specifically by a lymphocyte or an antibody
73
Define antibody
Antigen recognition proteins secreted by B cells
‘Antibody’- against foreign body
Y shaped structure with an antigen combining site at the tip of each arm that is identical
74
Describe the structure of the Y shaped Ig molecule
4 polypeptide chains held together by disulphide bonds
2 identical heavy chains and 2 identical light chains. N terminal regions of paired heavy and light chains form an antigen combining site
75
What are the different types of heavy and light chain
2 types of light chain: kappa and lambda
5 types of heavy chain: differ in amino acid sequences of their constant domains and are designated by the Greek letters u, y, a , E, theta = IgM, IgG, IgA, IgE and IgD
76
IgM antibody isotope
Mainly restricted to the blood stream because it is too large to diffuse readily across blood vessel walls (except in areas of inflammation)
77
IgG antibody isotope
Most plentiful class of Ig in the blood (also found in tissue fluids).. transferred across placenta from mother to foetus because of IgG binding receptor expressed by placenta - provides much of the early immune protection for neonate
78
IgA antibody isotope
Present in blood and internal tissue fluids as monomers
Dimer is IgA is transported across mucosal epithelium into the mucosal secretions of the gastro-intestinal, respiratory and Genito-urinary tracts
79
IgE antibody isotope
Present at very low levels in the blood because most binds to specific receptors (Fc E R1) expressed by mast cells in tissues
80
IgD antibody isotope
Appears to function only as an antigen receptor on B cell surfaces and only very small amounts are secreted
81
What are defensins
Anti-microbial peptides that are directly damaging to certain microbes. Produced by various cell types including leucocytes and epithelial cells
82
How do antibodies interact with defence components
Can simply bind to antigens (neutralising the activities of bacterial toxins or viruses)
Can also act as intermediaries to activate other defensive components that can interact with the Fc regions of antibodies
- IgM and IgG antibodies can activate the complement system of proteins; phagocytes have Fc receptors (FcR) that bind IgG or IgA
- natural killer cells similarly bind IgG; mast cells have FcR specific for IgE
- eosinophils have FcR specific for IgG or IgE
83
Define complement
The name for a collection of about 30 proteins found in the circulation and in tissue fluids that were initially described by their ability to ‘complement’ the effect of antibodies
Activation of complement proteins is triggered by infection and immune activation and occurs as a cascade or chain reaction with amplification built in
84
What do the activation steps for complement proteins involve
Splitting of complement proteins into active fragments by enzymes formed from other complement proteins eg C -> Ca + Cb
85
What are phagocytes
Macrophages and neutrophils that engulf microbes and digest them intracellularly
They express pattern recognition receptors that enable them to bind microbes directly. They also have receptors for opsonins (proteins of the immune system that coat the surface of microbes)
86
What do eosinophils do
They mediate extra - cellular digestion when infective agents are too large to be engulfed by phagocytes eg parasitic worms
They express FcR that bind IgG or IgE and they also express CR
87
What are mast cells
Tissue cells that express high affinity FcR that bind IgE antibodies from surrounding tissue fluid
Mast cells become coated with IgE antibodies and therefore acquire the antigenic specificities of these antibodies
88
What happens when an antigen binds 2 or more IgE antibodies on a mast cells surface
Triggers the release of inflammatory mediators. This can also be triggered by the complement activation peptides C3a and C5a
89
What is released upon mast cell triggering
Granules which store preformed inflammatory mediators eg histamine, heparin, tryptase
Mast cell activation also induces the synthesis of newly formed mediators that are released over a longer period of time
90
What is inflammation
The collection of processes that amplifies the immune response at sites of infection by facilitating the movement of components of the immune system to these sites
Whole range of inflammatory mediators can be involved including products of the activation of complement, mast cells, macrophages and T lymphocytes
91
What is the inner / cytoplasmic membrane
Lipid bilayer interspersed with proteins - helps move small diffusable metabolites
92
What is the cell wall of a typical bacteria cell
Peptidoglycan
93
What is the function of pili in a bacteria cell
Adhesion- allow to stick to epithelium - prevents them from being washed away can maintain an environment in a host
94
What does a gram stain do
Differentiates bacteria on the basis of their cell wall structure
Gram result / shape and size of bacteria can be definitive for a particular genus of bacterium
Gram positive = thick cell wall
Gram negative = thin cell wall
95
4 functions of cell wall
- maintain rigidity and cell shape / structure (meshlike linked exoskeleton- peptidoglycan)
- maintains osmolarity (prevents osmotic lysis)
- survival (cell wall interacts with host membranes)
- cell division ( forms cross-wall separating 2 daughter cells)
96
How is the bacterial cell wall synthesised
Peptidoglycan precursor is synthesised inside the cell
Exported across the cell membrane
A site is created in the existing wall by enzymic action
The new nucleotide minus the terminal D-ala is encorporated
Cell grows
97
What are the features of mycobacterium
- modified peptidoglycan layer
- covalently attached to arabinogalactan polymer
- mycolic acid waxy coat
- poor gram stain
98
Describe the features of the cell membrane of a bacterium
```
Lipid bilayer- hydrophobic
Similar gram +ve and -ve bacteria
No steroids (except mycoplasma)
Ion transport and energy production
Mesosome
Electron transport
```
99
Function of spores
- cell survival in adverse conditions
- desiccation, heat, starvation
- gram +ve only eg bacillus spp/ All clostridium spp
100
Function of capsules
- protection against phagocytosis
- both gram +ve / gram -ve
- gelatinous material, polysaccharide / polypeptide
101
Characteristics of flagella
- cell motility
- 1-20; polar or peritrichous
- coiled in structure
- anchored in bacterial membrane
- made of protein (flagellin)
- important in chemotaxis
- movement by ATP
102
Characteristics of fimbriae (pili)
- smaller length and diameter
- +100
- peritrichous arrange
- protein (pilin)
- adherence (adhesin)
103
Physical growth characteristics for organisms
```
O2/CO2
Temperature
Water
PH
Light
Osmolarity
```
104
Describe the structure of a T cell receptor
Made up of 2 constant domains (alpha and beta) and 2 variable domains that make up the combining site and vary depending on the T cell
105
Describe the structure of the B cell receptor
Made up of 4 chains (2 heavy and 2 light) T cell receptor only has 2 chains
Has constant domains (heavy and light)
Also has variable domains (heavy and light)
Antigen combining site is made up of the VL and VH
B cell receptor also has 2 antigen combining sites but T cell receptor only has 1
106
Why is a T cell a hetero dimer
Made up of 2 chains
107
In a T cell receptor what is the antigen combining site made up of
The variable regions of the alpha and beta chains
108
What is the role of the CD4 T helper cells
They help other cells kill the pathogen: stimulate B cells to produce antibodies or stimulate macrophages to activate phagocytosis and killing
109
What determines the type of T cell produced for cytosolic pathogens and intravesicular pathogens
The MHC class
110
Describe the structure of MHC class I molecule
Made up of an alpha chain with 3 domains : alpha 1, alpha 2 and alpha 3 and a beta 2 microglobulin
The peptide binding groove that detects peptides from a certain virus is made up of the alpha 1 and 2 domains
111
Describe the structure of the MHC class II molecule
Made up of 2 chains : an alpha and a beta.
| Peptide binding groove is made up of B1 domain and a1 domain
112
What kinds of pathogens bind to MHC class I molecules as oppose to MHC class II and what are they presented to
Cytosolic pathogens bind to MHC class I and intravesicular pathogens bind onto MHC class II
Cytosolic pathogens are then presented to CD8 T cells and intravesicular pathogens are presented to CD4 T cells
113
Outline the processing of an antigen for HLA class I
Cytosolic pathogen undergoes degradation in the proteasome.
MHC class I is loaded in the endoplasmic reticulum.
CD8 cytotoxic T cell is activated
Virally infected cell is killed
114
How is the antigen processed for HLA class II
```
An exogenous antigen:
Pathogen is degraded into small peptides and transported into ER
HLA class II cannot be binded in the same way as class I because of the peptide binding groove preventing it
MHC class II leaves ER with invariant chain via golgi and invariant chain is degraded so peptides can be loaded into peptide binding groove
MHC class II is then binded to cell surface
```
115
What do Th cells do
Activate B cells to produce antibodies and stimulate phagocytic and killing activity of macrophages
116
What do Tc cells do
Kill tissue cells that have become infected by microbes
117
What is the difference between B cells and T cells in the fact of when they can bind antigens
B cels can bind microbial antigens in their natural form directly to their surface Igs, leading to the production of specific antibodies
TCR of T cells cannot interact directly with microbes but bind only to fragments of antigenic proteins
118
What does HLA class I protein consist of
```
A large alpha chain non covalently associated with a polypeptide called B2-microglobulin. A3 domain and B2M that are proximal to cell surface have amino acid sequences and structural homologise with the domains of immunoglobulins
A1 and a2 domains of the HLA class I a chain form a cleft or groove on the surface of the protein distal to the cell surface membrane that holds the antigen peptide so that it is available for interaction with a TCR
```
119
What does HLA class II consist of
2 similarly sized polypeptide chains called class II a and B chains. Each has an immunoglobulin like domain proximal to the cell surface membrane while the a1 and B1 domains distal to the cell surface membrane jointly form a peptide binding cleft that holds and antigen peptide for recognition by TCR
120
Processing of antigen for presentation by HLA class I
Endogenous protein antigens present in the cytoplasm are degraded in an enzyme complex called a proteasome; some peptides generated are transferred to the endo plastic reticulum via peptide transporter proteins. AA sequence associate with newly synthesised HLA class I molecules and are transported to cell surface where they are available for recognition by Tc cells expressing CD8
