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Immunology Flashcards

1
Q

Describe the structure of the thymus

A

Bi-lobed
Packed with proliferating lymphocytes
Medulla and cortex

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2
Q

What happens to the thymus during infection

A

No obvious change

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3
Q

What are Hassall’s corpuscles and where are they found

A

Fibroblasts for regulatory T cell development found in the thymus

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4
Q

What happens to the thymus with age

A

Decrease in output of new lymph (but total does not decrease)

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5
Q

Describe the bone marrow

A

Site of B cell and RBC production

Yellow fat surrounded by red marrow

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6
Q

What happens in the bone marrow during infection

A

Increase in white blood cell production

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7
Q

Describe the lymphatic system

A

Drainage system to collect antigens and filter through the nodes and return fluid to the blood
Antigen is likely to enter the lymphatic system

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8
Q

Draw/describe a lymph node

A

Kidney shape
Medullary sinus is surrounded by the T cell area with many germinal centres surrounding this
Lymphoid follicle surrounds this

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9
Q

What is a germinal centre

A

Area where B cell proliferate

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10
Q

What happens to the lymph nodes during infection

A

Lymph nodes become enlarged/swollen

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11
Q

What is the purpose of high endothelial venues and where can they be found

A

causes cells to move from the blood to lymph

Found in the lymph nodes

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12
Q

Which secondary lymphoid organ does not have many HEV

A

Spleen

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13
Q

What is the function of the spleen

A

Filters for antigens in the blood

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14
Q

Describe the structure of the spleen

A 
White pulp (WBC)
Red pulp (RBC)
Germinal centres
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15
Q

What happens to the spleen during infection

A

Larger follicles

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16
Q

Describe how epithelium is a secondary lymphoid organ

A

Mucosal and skin as a physical barrier
Mucosae-associated lymphoid tissue (MALT)
Lymph drains in villi

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17
Q

What are Peyer’s patches and where are they found

A

Large aggregates of B cells that contain germinal centres important for immune response found in the gut epithelium

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18
Q

What are microfold cells and where are they found

A

Cells that sample antigens to pass them to the Peyer’s patch in the gut

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19
Q

Which immune response cells are found in the skin

A

Epidermal langerhans cells
T lymphocytes
Macrophages
Dermal dendritic cell

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20
Q

Describe the process of extravasion

A
  1. Naive T cells rolls along the endothelium
  2. They bind to proteins and carbs along the epithelium
  3. HEV has chemokine bound to the cell surface
  4. Lymphocytes have receptors for this and binds to the receptor
  5. Lymphocytes deliver a signal to the T cell, changing the structure of integrin
  6. Integrin becomes high affinity binding and binds to the epithelium to stop movement
  7. Transport through epithelium
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21
Q

Describe a neutrophil

A 
Phagocytosis
40-75% of leukocytes
short-lived
circulates the blood
First cells recruited
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22
Q

What are NETs

A

neutrophil extracellular traps

Release of granules and chromatin to form extracellular fibres

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23
Q

Describe eosinophils

A

phagocytosis and granule release
Defence against parasites
Helps B cells in GALT (IgA production)

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24
Q

Describe basophils

A

Granule release

Acts as an APC for type 2 immunity

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25
Q

Describe monocytes

A

phagocytosis , killing, cytokine release, APC
less abundant
dispersed in tissue
Signal infection to soluble mediators
Become macrophages when the leave the blood

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26
Q

Describe mast cells

A

Phagocytosis, granule release (pro-inflammation), histamine and leukotrienes
Mucosal in the lung or connective tissue in the skin
Activation by complement products (anaphylatoxins)
vasodilation (red skin) and increased vascular permeability (inflammation)

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27
Q

Describe dendritic cells

A

APC and cytokine secretion
migration to lymph node
network site of infection
adaptive

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28
Q

Describe natural killer cells

A

10% of blood
Infected cell lysis, secretion of interferon gamma, activating and inhibitory receptors (NO antigen receptor), binds to opsonised cells
Large granulated lymphocytes (cytotoxic)
Bind to opsonised cells
Cancer and viral infections

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29
Q

What are soluble mediators

A

Small secreted proteins important in cell-cell communication that are generally local acting
Effective even in low concentration

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30
Q

What are the types of soluble mediators and what are their functions

A 
Interleukins - leukocyte communication
Interferons - anti-viral
Chemokines - chemotaxis
Growth factors - proliferation and differentiation
Cytotoxic - tumour necrosis factor
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31
Q

What is complement

A

Complex series of 30 proteins and glycoproteins
Major role in complimenting the activity of specific antibodies in lysing bacteria
Triggers enzyme cascade systems to give a rapid and highly amplified response

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32
Q

What are the secondary effector functions of immunoglobulins after binding

A

Complement activation
Opsonisation (promotion of phagocytosis)
Cell activation via antibody-binding receptors (Fc receptors)

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33
Q

What are hyper variable regions

A

there are 3 in antibodies: CDR 1,2,3)

CDS = complement determining regions that acts as binding sites for antigens

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34
Q

Define antibody affinity

A

The strength of the total noncovalent interactions between a single antigen binding site and a single epitope on the antigen

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35
Q

Define antibody avidity

A

The overall strength of multiple interactions between n antibody with multiple binding site and a complex antigen with multiple epitopes

Better measure of binding capacity

36
Q

Give examples of antibody-cross reactivity

A

Vaccination with cowpox induces antibodies which are able to recognise smallpox
ABO blood group antigens
Antibodies made against Microbial antigens on common intestinal bacteria may cross-react with carbs on RBC

37
Q

Describe IgG

A 
gamma heavy
Most abundant
Has 4 subclasses
Actively transported across the placenta
Major activator of the classical complement pathway (1&3)
Blood and extracellular fluid
38
Q

Describe IgA

A 
alpha heavy
2nd most abundant
2 subclasses
Occurs as a monomer or dimer
secretory 
Protects mucosal surfaces from pathogens
Across epithelia
39
Q

Describe IgM

A 
Micro heavy
First Ig synthesised after exposure
Multiple low affinity binding sites
Large pentamer
Agglutination and complement activation
Blood
40
Q

Describe IgE

A 
E heavy
Allergic reactions
Parasitic infections
Binds to mast cell receptors and basophils to release histamine
Very low levels
41
Q

Describe IgD

A

Delta heavy
Expressed in B cell development and activation
very low levels

42
Q

Give the actions of antibody-antigen

A 
Neutralisation
Agglutination
Opsonisation
Complement activation
Bound by cells expressing Fc receptors (innate immunity: phagocytes, NK cells)
43
Q

Describe the process of T cell dependent B cell activation

A
  1. Phagocytosis of the pathogen
  2. Pathogen broken down and displayed on the B cell and the dendritic cell via MHC II
  3. T helper recognises the presented antigen on the dendritic cell then finds the B cell with the same antigen
  4. Co-stimulatory molecules (CD28) provides more signalling
  5. T cells produce cytokines
  6. Lymphokine secretion
  7. B cell enters the cell cycle and produces clones with identical BCR
44
Q

What does class switching involve

A 
IgM and IgD are "weak"
When signals (lymphokines) are given from T helper there is a class switch
45
Q

Where does affinity maturation occur

A

Germinal centres

46
Q

Describe the process of affinity maturation

A

AID enzyme causes a mutation in the antibody coding genes of the B cells (somatic hypermutation)
Cells can become worse -> apoptosis
Cells can become better -> stronger antibodies -> plasma or memory cell

47
Q

Explain clonal selection

A

From a large population, 1 cell is activated via antigen binding to BCR which leads to proliferation (clonal selection). Division and differentiation is clonal expansion

48
Q

Describe the T cell independent activation pathway

A

A repetitive bacterial polysaccharide acts as the first signal
Microbial constituent or accessory cell provides second signal e.g. LPS

49
Q

What causes differences in Ig for T cell independent and dependent

A

No lymphokines released in T cell independent

50
Q

Describe the TCR

A

The Fab region of an antibody, top is variable, bottom is constant. One alpha and one beta and a cytoplasmic tail.

51
Q

What is the difference between the alpha and beta chains of the TCR

A 
alpha = V and D and 1 recombination
Beta = V, D and J and 2 recombinations
52
Q

What are CD4 and CD8 and where are they found

A

Co-receptors that bind to MHC.

CD4 is found one T helper cells while CD8 is found on T cytotoxic cells

53
Q

What is HLA and where is it found

A

Human leukocyte antigen - genes found in all vertebrates that code for MHC. polygenic
Chromosome 6
co-dominant expression

54
Q

Relationship between HLA and MHC

A 
MHC class I = A,B,C
MHC class II = DP, DQ, DR
55
Q

What is haplotype

A

Group of MHC alleles on 1 chromosome

56
Q

Describe the endogenous MHC pathway

A

MHC I. Synthesised in the cytoplasm

  1. TAP transports protein to RER
  2. calnexin and calreticulin and tapasin fold and stabilise the MHC
  3. molecules transport to the golgi
57
Q

Describe the exogenous MHC pathway

A

MHC II. Antigens from external environment

  1. invariant chain stabilised the MHC complex
  2. transport to the golgi
  3. invariant chain is digested to leave a CLIP
  4. Antigen is endocytose and broken down
  5. Peptide presented on MHC
  6. MHC exocytosed
58
Q

Why may antibodies be inefficient

A 
Pathogens:
Can hide within cells
Can change antigen shape
Can coat the antigen with antibodies
Can produce fake antigens
59
Q

What are T cells defined by

A

inputs (STAT) and outputs (cytokines)

60
Q

How do killer T cells induce apoptosis

A

Granule release - Perforin, granzyme, granulising
Fas ligand - binds to Fas receptor on the cell
Release of caspases to drive apoptosis

61
Q

What are the activation steps of a naive T cell

A
  1. TCR/CD8 - MHC I Binding
  2. CD28 co-receptor activation
  3. cytokines from infected cell
62
Q

What is Th1 involved in

A

Macrophage activation
Delayed type hypersensitivity
B cell activation
Regulation

63
Q

What occurs when the macrophage cannot kill the pathogen e.g. tuberculosis

A
  1. Cytokine release
  2. endothelial cells express proteins
  3. Monocyte and Th1 migration
  4. Th1 activates monocyte and macrophage
64
Q

What is the process of Th1 amplification

A
  1. Activated Th1 binds to MHC II and CD40 on the B cell
  2. Secretion of IFN gamma
  3. Upregulation of MHC II, CD40 and tumour necrosis factor alpha
  4. Increase in TNF alpha secretion (autocrine) from macrophages
  5. amplification
65
Q

Give features of Tfh

A

Activation by dendritic cells
Stimulates B cells
Generation of isotope-switched antibodies

66
Q

Describe tuberculosis

A

Ingested by macrophages
TB inhibits phagosome -lysosome fusion and lives in macrophages
Granuloma formation contains the infection

67
Q

What is the role of Th2

A

Targets and stimulates eosinophils
Trigger in tracheal epithelia
Travels from dendritic to naive

68
Q

What CD marker is expressed on naive memory T cells

A

CDC45RA+

69
Q

What CD is expressed on central memory cells

A

CCR7

70
Q

What is the function of Treg

A

Regulation of T cells and tolerant of self-antigens

secretes immune-suppressive cytokines and inactivates dendritic cells

71
Q

What is the function of Th17

A

Interleukin 17, bacterial control and neutrophil recruitment

72
Q

Describe the process of T cell development

A

Produced in the bone marrow (CD4-CD8-TCR-)
In the cortex = CD4+CD8+TCR+
In the medulla = CD4+CD8-TCR+ vice versa

73
Q

Describe selection in the thymus of T cells

A

Thymocyte can’t bind = apoptosis
Weak binding = survival (+ve selection)
Strong binding = apoptosis (-ve election)
Prevents autoimmunity risks

74
Q

What is the purpose of Interferon type 1

A

Activation of NK

75
Q

What is the purpose of interferon type 2

A

Produced by T cells pre-inflamamtion

76
Q

Define cytokine storm

A

Over production of cytokines and accumulation of cells

77
Q

What are the main modes of pathogen transmission

A

Respiratory - large SA
GI tract - large SA
Zoonosis
Sexually transmitted

78
Q

Define pathologic

A

Immune response against a self antigen, often classified under immune mediated inflammatory diseases

79
Q

Define pathogenesis

A

susceptibility genes and environmental triggers

80
Q

Describe hypercytokinaemia

A

Too much immune response
positive feedback loop
pathogens enter the wrong compartment e.g. the blood (Sepsis) or failure to regulate response to the correct level

81
Q

What is the 3 signal model

A

Licensing a response

  1. Antigen recognition
  2. Co-stimulation
  3. Cytokine release
82
Q

How is immune response controlled

A

Responses against pathogens decline as the infection is eliminated

83
Q

Compare central to peripheral tolerance

A

central - destroys self-reactive T or B cells

peripheral - destroy or control self-reactive cells that do enter circulation

84
Q

What is AIRE

A

AutoImmune Regulator

A gene for a specialised transcription factor that allows expression of genes in peripheral tissues for self tolerance

85
Q

What is the function of IL-10

A 
Master regulator
Shuts down dendritic cells
Pleitropic (multifunctional)
Blocks pro-inflammatory cytokine synthesis 
Downregulates macrophages
86
Q

What are the main mechanisms of peripheral tolerance

A

Anergy - APC presents the antigen but the T cell is shut down
Deletion - apoptosis of the T cell
Ignorance - less APCs
Regulation - regulation of the response by cytokines from Treg

?? (14 decks)

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