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Immunology Flashcards

1
Q

What are the functions of a macrophage

A
  1. Debridement/ removal of injured tissue and debris (phagocytsosis, collagenase, elastase)
  2. Chemotaxis and proliferation of fibroblasts and keratinocytes
  3. Angiogensis
  4. Deposition and remodelling of ECM
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2
Q

What cell orchestrates tissue repair

A

Macrophages

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3
Q

What host factors influence inflammation and repair (5)

A

Nutrition
- Protein, vitamin C

Metabolic status
- Healing is slower in diabetics

Steroids
- Anti-inflammatory and slow collagen synthesis

Infection
- Most important cause of delayed healing

Mechanical factors
- Excessive movement slows healing

Blood supply
- Impaired in diabetics and other disorders

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4
Q

Do dead cells stain more pink or purple

A

Stain deeper pink (E) due to increased eosinophils, and loss of RNA decreases the purple (H)

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5
Q

What are the major components of innate immunity

A
  • Activation of alternative complement pathway
  • Phagocytosis
  • Acute phase proteins
  • Natural killer cells (In intracellular)
  • T and B cells not involved (with the exception of IGM antibodies)
  • Inflammatory response exemplifies the innate response.
  • Little specificity
  • Same reaction each time
  • No memory
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6
Q

Outline the role of macrophages in acute inflammation (extracellular i.e bacterial infection)

A
  • Constantly surveying environment phagocystosing and looking for danger signals.
  • To activate a macrophage you need 2 steps.
    1. Phagocytosis
    2. Danger material
  • Toll like receptors (inside macrophages detect danger materials).
    = activation of inflammation

Once activate they make THREE critical cytokines.
- IL-8: Goes to the bone marrow and recruits NEUTROPHILS (chemokine)
- TNF alpha and IL-1, alter endothelial wall to allow neutrophils to stick to it and enter tissue (Margination and diapededesis)
- i.e they make the endothelial cells express receptors (activation) and the neutrophils also have the same receptors/ appropriate adhesion molecule

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7
Q

CD nomeculature

A

Polypeptide on surface of cells that induce the formation of antibodies.
May be exclusive to a cell type of broadly distributed.

  • CD3 = T cell
  • CD4 = Th cell
  • CD8 = Tc cell
  • CD19 or 20 = B cell
  • CD11c = DC
  • CD56 = NK cell
  • CD14 = Monocyte
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8
Q

What is the complement cascade

A

Complement - a series of 9 major proteins which act in sequence to clear potentially pathogenic material from blood and tissues.

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9
Q

What is the function of the complement cascade

A

Central aim: to split C3, the most abundant
complement component, to generate the components that

– opsonise microorganisms (labels them)

– degranulate mast cells to release
chemotactic+inflammatory mediators
(e.g.histamine) (i.e chemotaxis)

– assemble the ‘membrane attack complex’ (MAC) which causes perforations (i.e destroy)

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10
Q

What are the 3 complement pathways

A
  • Alternative pathway/bypass (LPS)
  • Lectin pathway
  • Classical pathway (antibody)
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11
Q

Describe how the alternate and lectin pathways activate complement

A
  • Complement is an inert protein present everywhere.
  • It gets activated by LPS and other moietes on bacteria.
  • Enzymes chop up C3 and C5 into C3a, C3b, C5a, C5b.

C3a and C5Aa then release IL-8 (chemotactic) and result in the degranulation of mast cells (vasodilation). THIS IS NOT THE SAME AS ANAPHYLAXIS

C3b = Helps speed up phagocytosis (Opsonisation!)

C5B = Binds, to 6,7,8 + ring of C9 (MAC), which essentially punches a hole in bacteria (osmotic lysis).

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12
Q

Receptors that clear complexes containing C3

A
  • CR1: on RBC, monocytes, granulocytes, B cells - provide
    entry for mycobacteria, leishmania
  • CR2: on B cells - provide entry for EBV, and HIV
  • CR3: on macrophges, NK cell and polymorphs -
    provide entry for mycobacteria
  • CR4:

(lots of ways for viruses to target complement and invade a cell)

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13
Q

What type of bacteria is the complement pathway particularly important in treating

A

Gram negative

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14
Q

How do we protect host cells from the effects of complement?

A

Membrane-bound complement inhibitors on cells include:

DAF (decay accelerating factor) and MCP (membrane
cofactor protein) which break down C3 convertase

HRF (homologus restriction factor) C8 binding protein and CD59 which prevent the formation of MAC on host cells

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15
Q

What are the vascular reactions in acute inflammation

A

Vasodilation and an increase in vascular permeability

  • NO, histamine, serotonin
  • Vessels affected are arterioles, capillaries and
    venules at site of infection.
  • Cells get pulled apart
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16
Q

Mediators in acute inflammation

A

Histamine
Serotonin
Prostaglandins
Leukotrines
PAF
ROS
NO
Cytokines
Neuropeptides

Complement
(C3a, C5a, C3b, C5b-9)

Kinin system
Coagualtion/fibrinolysis

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17
Q

What are acute phase proteins and what are their function

A
  • Fibrinogen (helps wall off infection via fibrin)
  • CRP-1 (Helps chop up complement)
  • Haptoglobin (Reduces availability of iron to bacteria)
  • Mannose binding protein, amyloid a, serum amyloid P, C’ proteins and coagulation proteins
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18
Q

What are natural killer cells

A

Essentially just granular lymphocytes

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19
Q

What stimulates the release of acute phase reactants

A

TNF goes to the liver

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20
Q

Which cytokine is responsible for fevers

A

IL-1

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21
Q

Outline the early response to viruses (i.e how they get into cell and what they do inside)

A

Viruses have to bind to a cell surface receptor (sometimes a complement receptor).

They then gain access into the cell then they can replicate and lyse cell.

Once inside they try to hide from cytotoxic T cells. They do this by down-regulating the expression of MHC1 (or killing activator). As ALL nucleated cells express MHC1.

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22
Q

What is a natural killer cell and how do they get activted.

A

Essentially the viral version of a macrophage.

Alternatively called large granular lymphocytes.

Their activity is inhibited when they see MHC1 on target cells.

  1. THEREFORE they recognise when cells infected with viruses have down-regulated MHC1 (to try and escape cytotoxic T cells).
  2. They have CD16 Fc receptors for igG
    - I.e they can acquire an antibody and allow antigen specific recognition
    - This is called anti-body dependent cell mediated cytotoxicity
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23
Q

Can you tell the difference between lymphocytes under the microscope.

A

No B cells and T cells look the same.
They have a very large nucleus compared to cytoplasm.
NK cells however have granulocytes so you can differentiate them on the blood smear.

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24
Q

Two ways that NK cells result in apoptosis.

A
  1. Upon activation, NK cells release cytotoxic granules containing perforin and granzymes to directly lyse tumor cell.
  2. Activated NK cells express FAS ligand which interacts with FAS on APC (extrinsic pathway)

(same mechanisms as Tc cells)

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25
Q

Where are lymphocytes made

A

All lymphocytes are made in the primary lymph tissue
- T cells: Thymus
- B cells: Bone marrow

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26
Q

Describe T cell development in the thymus

A

All T cells begin as double negative.

I.e they do not have CD3, CD4, or CD8.

They then begin to express T cell receptors. CD3 (alpha/beta OR delta, most are alpha or beta), CD4 and CD8. They have now gone from being double negative to double positive.

They then drop EITHER CD4 or CD8 to become T helper or cytotoxic T cell.
CD4 = helper CD8 = toxic

They then learn how to recognise MHC and learn to not respond to self peptide before being exported to the periphery.

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27
Q

How many T helper cells do you get for each cytotoxic developed

A

2

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28
Q

Which T cell recognises which MHC

A

CD8 = MHC1
CD4 = MHC2

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29
Q

What antibody do all B cells express

A

IgM

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30
Q

How do lymphocytes enter the lymph nodes and the spleen

A

Via the blood or via the AFFERENT lymph
Only enter spleen via the blood

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31
Q

Where are B cells and T cells located in the lymph node and spleen

A

They are separated out.

Lymph node
- T cells: Paracortex (centre)
- B cells: Outer cortex

Spleen
- T cells: Inner region of PALs (DC here)PA
- B cells: Marginal zone or outer region of PALS

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32
Q

What cell is responsible for activating T cells and how/where does this occur.

A

If the stimulus persists and we haven’t been able to clear the infection with the innate immune response.

Dendritic cells will start getting ready to interact with T cells.

Only happens in the lymph not in the periphery.

Dendritic cells are responsible for priming T cells.

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33
Q

How do we present antigens to cells

A

If APC is phagocytosing cells we get MHCII interacting with Thc (CD4) (naive)

If APC is cystolic derived we get MHC-1 and cytotoxic T cell CD8

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34
Q

What is an antigen

A

Any substance that can bind to an antibody and generate and immune response (i.e immunogen)

OR react with antibody/T cells but do not generate an immune response
e.g hapten which can only generate a response if it is couple to a carrier CNP

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35
Q

Are antigens big or small

A

Generally high molecular weight but can have low molecular weight carbohydrate antigens

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36
Q

What is an epitope

A

Small part of an antigen recognised by the antigen combining site of an antibody (paratope) or a T cell receptor.

Comprises 6 amino acids of linear protein or up to 21 amino acids of a globular protein

(conformation important -degradation = no
recognition)

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37
Q

Do TCR and B cells recognise the same epitope

A

Not necessarily

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38
Q

What is MHC/HLA

A
  • It is the molecule that presents antigens to T cells (derived from inside or outside the cell)
  • Conserved in evolution
  • Essential for recognition of a foreign antigen
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39
Q

What chromosome is HLA coded on, how many regions are there, what are the products of each region

A

Short arm of chromosome 6

Class 1 region
- A, B, C, E

Class II
- Putative peptide transported
- DP, DQ, DR

Class 3
- HSP70
- C2 and C4

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40
Q

Is HLA polymorphic and explain the implication

A

Yes, very polymoprhic
This means it can express millions of different peptides

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41
Q

How is HLA Expressed, compare this to B cells and explain the implication

A

HLA is co-dominantly expressed.
This means that both copies you get from your parents are expressed (instead of one or the other), this means that you can present even more peptides.

(Unlike B cells when you can only express one antibody e.g IgG or igA)

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42
Q

Outline the structure of MHC

A
  • Heterodimer (an alpha and a beta chain)
  • On MHC1 - the alpha chain forms the peptide binding groove and has a b2 microglobulin which stabalises the alpha chain has 1 cytoplasmic tail
  • On MHCII the alpha chain and the beta chain, has 2 cytoplasmic tails. MHCII is bigger than MHC1 therefore can hold a bigger peptide.
  • MHC look similar to T cell receptor
  • NOT biochemically similiar to B cell receptor
  • To be stable they have to have a peptide in their binding site (most of the time this is just self peptide)
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43
Q

How is HLA passed on

A

In blocks, i.e the offspring of 2 parents can only give 4 different combinations
(linkage disequilibrium)

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44
Q

What is MHC restriction

A

A T cell recognizes antigen as a peptide bound by a particular allelic variant of an MHC molecule, and will not recognize the same peptide bound to other MHC molecules.

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45
Q

How do we activate Th cells

A

Requries 2 signals

Signal 1: Interaction between MHC and peptide complex

Signal 2: Co-stimulatory molecules.
CD80/86 (dendritic): CD28 (Tcell)

Activation of antigen presenting cell required to induce co-stimulatory molecules (danger signals)

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46
Q

Outline the structure and function of a T cell receptor

A
  • Any naive T cell expresses a UNIQUE receptor for a specific antigen.
  • All receptors on that T lymphocyte will be the same
    I.e CAN ONLY REACT TO ONE ANTIGEN
  • NOT secreted (unlike B cell receptor/antibody)
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47
Q

How many gene segments are required to make a BCR and TCR

A

7

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48
Q

What segments are on the alpha chain of a TCR and what are on the beta chain

A
  • V,J and C region (a chain)
  • V,D, J and C (b chain)
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49
Q

Do TCR show generation diversity

A

Yes the different segments are spliced and transcribed etc

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50
Q
  • Examples of superantigens
  • Where do superantigens bind
  • How many T cells do they activate and what implication does this have
  • Symptoms associated
A
  • Staph aureus enterotoxin
  • Strep pyogenes exotoxin
  • Bind to TCR and MHCII outside of usual peptide binding site
  • Activate up to 20% of T cells, which results in massive production of IL-2
  • Toxic shock syndrome, fever, nausea, diarrhoea, malaise.
51
Q

What are polyclonal activators

A

These activate T or B cells in the absence of any contact with antigen.
Sometimes referred to as mitogens because they stimulate mitosis
They are important because

  1. they may underlie the hypergammaglobulinaemia of AIDS, and also the B cell neoplasia that sometimes follows EB virus infection in immunosuppressed patients
  2. their use in assessing T and B cell function

T cells
- Antibody to CD3
- Concanavalin A
- Pokeweed mitogen

B cells
- Antibody to immunoglobulin
- Staph aureus (Cowan strain)
- EBV
- Pokeweed mitogen

52
Q

What are the 3 important T helper cell subsets, what cytokines do they release and what do they defend against.

A

TH1
- IFN gamma, TNF alpha, IL-12
-Viral/ TB, MS, RA, Chrons

TH-2
- IL-4, IL-5
- Worms
- Anaphlaxis (type 1 hypersensitivity)

TH17
- Cytokine produced - IL-17
- Bacterial/ fungal disease

53
Q

What are the 2 subsets of B cells and what are the differences.

A

B1 and B2 subset - both of which express surface immunoglobulin

B1 subset
- Respond to antigens without T cell help (T cell independent i.e have never interacted with a T cell)
- Antibody is restricted to igM isotype
- Do not produce memory cells
- Express CD5

B2 subset
- Respond to T dependent antigens (i.e have interacted with a T cell before)
- Undergo class switching so all isotypes of antibody can be produced
- Produce memory cells (have to become an APC to do this)
- Do not express CD5

54
Q

Describe the key lymphocyte responses for a bacterial primary infection

A

First we get 2 step activation of T cells (by DC)
- i.e MHC/peptide AND Co-stimulatory molecules.

THEN

Activated T helper cells secrete IL-2.
- This results in clonal proliferation of T helper cells.

Dendritic cell then secretes cytokines that tell it what type of T helper subset to become (Th1, Th2, Th17) which then release their OWN cytokines and they express CD40 (marker of activated T cell).

AT THE SAME TIME
Naive B cells (secreting igM) recognise bacteria.
B cells chop up bacteria and present peptides to T helper cells.

B cells are then activated in a TWO step process.
- MHCII/peptide/TCR AND
co-stimulatory molecule CD40 ligand and CD40L)

B cells can then start undergoing seroconversion and making specific immunoglobulins NOT igM (igG , igA or igE)

55
Q

How do we know when T helper cells are effector

A

When they start expressing CD40 and secreting their specific cytokines.

56
Q

How long does it take T helper cells to become effector

A

4-5 days

57
Q

How long does it take B cells to undergo seroconversion

A

2 weeks

58
Q

What are the different antibody classes and subclasses

A

igA
igM
igE
igD
igG

59
Q

Which immunoglobulins activate complement

A

igM
igG3, igG1, igG2 (NOT igG4)

60
Q

Which immunoglobulins have high affinity

A

igG has highest, igE, igA also have high affinity

61
Q

What is avidity and what immunoglobulins have high avidity

A

Avidity is how many sites it can bind to.
igG has low avidity
igM has high avidity

62
Q

Which immunoglobulin can cross the placenta

A

igG (number 2 is the least effective at doing this).

63
Q

Which immunoglobulins have J chains

A

igM and igA dimer

64
Q

Which immunoglobulin is fixed to mast cells

A

igE

65
Q

Which immunoglobulin has a secretory piece

A

igA dimer

66
Q

Which immunoglobulin can become a dimer (the rest being polymers)

A

igA

67
Q

What is the structure of igM

A

Pentameric

68
Q

Describe the key characteristics of cytokines

A
  • Soluble intracellular messengers
  • Low molecular weight, secreted proteins
  • Produced by a diverse range of cells
  • Act autocrinally, paracrinally or at a distance
  • Effective at very low concentrations
  • Transient
  • Pleiotrophic (Multiple actions on multiple cells, never do just one function!)
  • Act on specific receptors
  • Act synergistically (TNF and IFN) or antagonistically (IL-4 and IFN gamma)
69
Q

What is the function of Il-1 and what cells produce it

A
  • Proliferation of activated T, B cells.
  • Induction of Il-6, IFN gamma, GMCSF
  • (+ its effects in the innate immune system)

Produced by macrophages and fibroblasts

70
Q

What is the function of IL-2 and where is it produced

A
  • Growth of activated T and B cells
  • Activates NK cells
  • Produced by T cells
71
Q

What is the function of IL-3 and where is it produced

A

mast cell growth
growth +differentiation of haemopoietic precursor cells

Produced by T cells, macrophages

72
Q

What is the function of IL-4 and where is it produced

A

isotype switching (IgGl->IgE)
characterises Th2 subset

Produced by T cells and mast cells

73
Q

What is the function of IL-5 and where is it produced

A

igM, igA production, eosinophil and activated B cell proliferation

Produced by TH2 subset, mast cells

74
Q

What is the function of IL-6 and where is it produced

A

Induction acute phase proteins, growth+differentiation hematopoietic cells

Produced by macrophages, Th, mast cells and fibroblasts

75
Q

What is the function of GM-CSF and where is it produced

A

Colony growth, activates macrophages, neutrophils and eosinophils

Produced by macrophages, T cells, endothelium and mast cells

76
Q

What is the function of TNF-alpha and where is it produced

A

Activates macrophages, tumour cytotoxicity, cachexia

Produced by macrophages and T cells

77
Q

What is the function of TNF and where is it produced

A

Induces acute phase proteins, anti viral/ anti parasite activity, activates phagocytes, induces pro-inflammatory cytokines

Produced by CD4 T cells

78
Q

What is the function of IFN alpha and where is it produced

A

Anti viral, up-regulates MHC-1

Produced by leucocytes

79
Q

What is the function of IFN gamma and where is it produced

A

Anti viral, macrophage activation, upregulates MHC, simulates CTL differentiation, antagonizes IL-4, characterises Th1 subset

Produced by T cells

80
Q

Where is the secretory piece added to igA

A

Mucosal epithelium

81
Q

What are the 2 types of igA and where are they found

A

Monomer - Blood
Penatemer - Mucosa (neutralises virus on reinfection and activates killing cell

82
Q

3 HLA typing techniques

A

PCR
flow cytometry
complement-mediated cytotoxicity assay
- Lymphocytes taken from blood and are mixed from antibody (from host or manufactured). Both B cells and other lymphocytes are used.
- Complement is then added and kill cells if the antibody and leucocyte have bound.

83
Q

Describe the structure of an antibody

A

Y shaped structure consisting of 2 heavy chains and 2 light chains.

Contains both intra- chain and interchain disulphide bonds

The light chains are either kappa OR delta.

Further subdivided into Fab and Fc regions.

The Fab region contains the light chain (which is made up of one part constant and one part variable) and half of the heavy chain (which is one part variable and 3-4 parts constant)

FC region

Composed of heavy chain constant domain only.

Interacts with cell surface receptors

It is the constant domain of the heavy chain that determines the isotype. This is also where complement binds

84
Q

How do microbials evade the immune system

A
  • Antigenic variation
  • Mutation
  • Escape into the cytosol
  • Preventing complement activation
  • Slippery carbohydrate capsules
  • Repelling phagocytes
  • Down regulating MHC I
  • Production of downregulatory molecules
  • Impairing interferon production
85
Q

What are examples of live attenuated vaccines and who cant we use them in.

A

Options for immunising antigens

Live attenuated organisms
– bacterial: BCG vaccine
– viral: Sabin (polio), measles, mumps

Constraint: Never administered to immunologically compromised individuals.

86
Q

Examples of non replicating vaccine targets

A
  • Non-replicating, dead organisms
  • bacterial:
    typhoid
    cholera
    pertussis
  • viral
    Salk (polio)
    influenza
87
Q

What are examples of sub unit vaccines

A

Viral
- hepatitis B
- influenza (recombinant antigens)

Bacterial:
- Haemophilus influenzae (Hib) - bacterial
- capsulate polysaccharide conjugated to Neisseria meningitidis protein
- tetanus toxoid
- diptheria toxoid
- Streptococcus pneumoniae, bacterial polysaccharide

88
Q

What are adjuvants

A
  • Any substance that non-specifically enhances the response to an antigen
  • Adjuvants are injected simultaneously with dead organisms or vaccine antigen.
  • Produce depots of antigen
  • Activate antigen presenting cells
  • Alum only adjuvant licensed for clinical use
89
Q

Outline the immunisation schedule for splenectomy

A

Bacteria responsible for overwhelming
post-splenectomy infections:

  • Strep. pneumoniae
  • Nesseria meningtidis
  • Haemophilis influenzae

Immunisation against these required before elective splenectomy ->2weeks prior

90
Q

What is passive immunity

A
  • Host receives antibodies from another individual
  • No memory
  • Immunity short lived
  • Immune reaction to antibodies possible
91
Q

What is adoptive immunity

A

Transfer of lymphocytes from an immune to a non-immune individual

  • Destroyed in genetically non-identical hosts
  • GvH in immunocomprised individuals
92
Q

What is an autogenic transplant

A

Autogeneic transplant: graft taken from one site transplanted to another on the same individual
- accepted.

93
Q

What is an allogenic transplant

A

Allogeneic : graft from a donor from same
species but not genetically identical -rejected.

94
Q

What is a syngeneic (isograft)

A

graft from donor that
has same genetic composition as recipient -
accepted.

95
Q

What is a xenogeneic transplant

A

graft from different
species- rejected.

96
Q

What occurs in an allogenic transplant rejection

A

Mostly a T cell mediated response

97
Q

What segments combine to encode a complete antibody.

A

7 gene segments

Heavy chain
V
D
J
C

Light chain
V
J
C

98
Q

What forms the antigen binding segment

A

VDJ (heavy) and VJ (light)

99
Q

Which gene segments predominates in an antibody

A

V

100
Q

What determines isotype

A

5 heavy chain C gene segment

101
Q

What are the Fc receptors for IgG

A

CD64
- Constitutively expressed on monocytes, macrophages (inducible on neutrophils and eosinophils)

CD32
- On all hematopoietic cells except RBC - sole form of
FcR on some cells e.g. platelets

CD16
- Mediates ADCC by NK cells

102
Q

Compare lymphocyte reaction to alloantigens compared to extraneous peptides (and explain why this occurs)

A

Approximately 10% lymphocytes react to
allo-antigens compared with about 1:10,000 to extraneous peptides.

  • Structure of MHC peptide binding groove varies
    between individuals due to MHC polymorphism
  • Different range of peptides accommodated by MHC on donor versus host cells
  • Self’ peptides (normally not recognised by the
    host) may be recognised in context of donor MHC
103
Q

What HLA is more important to match

A
  • HLA-A,-B not essential but beneficial
  • HLA-DR region more important than MHC I
104
Q

Compare indirect and direct antigen presentation in allogenic grafts

A

Direct
Donor dendritic cells (graft cells) travel to host Lymph node, present allogenic peptides and triggers T helper cell activation).

Indirect:
Host dendritic cells infiltrate graft, sample alloantigen released from donor cells, return to the lymphoid tissue to present this to host T cells.

105
Q

What are naturally occuring T regs

A

CD
CD25
FoxPe

They control T cell proliferation by production
of IL-10 and TGFβ

(example of peripheral tolerisation)

106
Q

7 Features of autoimmune disease

A
  • Presence of autoantibodies
  • Lymphocyte, macrophage and plasma cell infiltration
    into lesions
  • Presence of more than one autoimmune condition
  • Female bias
  • Occur in families
  • HLA associations
  • Lesions classified by hypersensitivity Types II,III,IV
107
Q

How can we subdivide autoimmune conditions

A

Local vs systemic

108
Q

What is X linked Agammaglobulinemia

A
  • Also called Brutons disease
  • One of the more common forms of primary immunodeficiency
  • Failure of pre B cells to develop into B cells
  • Antibody molecules are not formed properly in the disease and therefore patients do not produce immunoglobulin
  • Also see a significant reduction in B cell numbers in the blood
109
Q

Effects of B cell deficency

A
  • Increased susceptibility to pyogenic infections (reduced opsonisation by
    antibody -> impaired phagocytosis)
  • Impaired response to bacterial toxins
  • Graft rejection and DTH normal
110
Q

Examples of secondary immunodeficienes

A
  • autoimmune disease
    – neoplasms
    – accompanies measles, chicken pox, mumps,
    severe trauma leprosy, Hodgkins disease
    – malnourishment
    – HIV-AIDS
111
Q

What is DiGeorge Sndyrome

A
  • Patients have no thymus gland
  • As a result patients have no development of T cells within the thymus
  • Patients are very susceptible to infection. They
    can’t mount a cell mediated response and can’t induce switching of antibody

Note: you can get a partial DiGeorge syndrome whereby patients have an
extremely small thymus

112
Q

What is SCIDS

A
  • Stem cell disorder
  • Results in no B cells or T cells in patient
  • Two most common forms are ADA deficiency and common γ chain mutation in cytokine signaling
  • ADA (adenosine deaminase) is an enzyme
    involved in purine metabolism
  • Cytokine signaling mutations results in no
    growth factors for cell survival
113
Q

Features of innate immune deficiencies

A

Defective production of polymorphs
- Defective response to chemotactic stimuli
(Lazy lymphocyte syndrome)
- Defective leucocyte adhesian (LFA-1 defect)
- Defective lysosomes, in polymorphs (pyogenic infections)
- No production of reactive oxygen
intermediates

114
Q

Outline the key steps involved in responding to a virus

A

Dendritic cell goes to Lymph node and present viral peptide on MHCII with CD80 and 86 to T cells that have the right receptor (CD28).
T cells makes Il-2 which results in a TH-1 response. TH-1 cells release TNF and INF which make cytotoxic T cells stronger.

They can also present on MHC-1 and interact with Cytotoxic T cells presenting Cd8. This also produces IL-2. Il-2 then

115
Q

Phagocytosis is enhanced as a result of …

A
  1. activation by IFNy (interferon gamma) this is an important part of TH1 responses
  2. adherence of IgG antibodies
  3. fixation of complement by IgM antibodies

Note that macrophages do not have receptors for IgM, but have complement receptors and phagocytose IgM antibodies that have fixed complement by virtue of these

116
Q

Clinical features of DiGeorge and how to treat

A

partial Di George syndrome is more common than the complete syndrome

Di George syndrome is characterized by mal-development of 3rd & 4th pharyngeal pouches, leading to Thymic hypoplasia or aplasia primary T cell deficiency

  • Parathyroid hypoplasia: abnormal Ca regulation with hypocalcemic tetany

congenital defects of heart and great vessels

dysmorphic facies

if children survive into their fifth year, T-cell function tends to normalize even with thymic aplasia

A well-matched thymus transplant could be expected to correct the immunodeficiency

117
Q

What type of antibodies are ABO and what are they post incompatible transfusion

A

Usually IGM

only after incompatible transfusion are they likely to be IgG

118
Q

Positive tuberculin test in a 30 year old woman indicates

A
  1. that she capable of mounting a delayed hypersensitivity reaction
  2. is unlikely to be suffering from a T cell immunodeficiency
  3. is manifesting a secondary response to tuberculoprotein
  4. has almost certainly encountered liver mycobacteria previousy
119
Q

Horse serum administered to man may bring about

A
  1. passive immunity
  2. anaphylaxis
  3. a primary response
  4. serum sickness
120
Q

Give other examples of immunodeficiency (i.e not T and B cell)

A

NK cell deficiency:
- Very rare, but patients lacking NK cells have had life threatening virus infections with EBV, varicella and CMV.

Complement deficiencies:
A variety of bacterial infections (often involving Neisseria) and immune complex diseases have
been described.

Defective phagocytosis:
Several disorders have been described
- Defective production of polymorphs
- Defective leucocyte adhesion
- Defective chemotaxis
- Failure of cellular oxidative reaction

121
Q

How to test B cell competence

A
  • Measure total serum immunoglobulins (below 2 g/l =immunodeficiency).
  • Determine the proportions of the different antibody classes (approximate normal % = IgG 80%,
    IgA 13%, IgM 6%, IgD 0-1%, IgE <0.002%).
  • Count circulating B cells (identified by surface immunoglobulin).
  • Determine whether B cells proliferate on exposure to polyclonal activators such as pokeweed mitogen (PWM).
  • Examine B cell areas of lymph nodes and look for plasma cells.
  • Measure levels of natural antibodies (eg to ABO antigens, to sheep red cells).
  • Test whether antibody is produced on suitable immunisation - but NEVER use live vaccines in immunodeficient hosts (because of the risk of opportunistic infection).
122
Q

How to test T cell competence

A
  • Count the T cells in blood (using anti-CD3 which identifies all T cells).
  • Determine the ratio of CD4 (TH) to CD8 (TC) cells - normally about 2:1 (ratio is low in AIDS).
  • Test the ability of T cells to multiply in response to polyclonal activators such as the lectins phytohaemagglutinin (PHA) and concanavalin A (con A).
  • Test the ability of T cells to proliferate in the presence of MHC incompatible cells (the mixed lymphocyte reaction - MLR).
  • Examine the cellularity of T cell areas in lymph nodes and elsewhere.
  • Test delayed hypersensitivity responses (which depend on Th cells) using tuberculin, mumps Ag
123
Q

Immunosuppression drugs that impair T cell function

A
  • Azathioprine
  • selectively targets T cell mediated reactions via its active active metabolite ribotide, which (-) the synthesis of nucleic acids
  • anti-CD3 monoclonal antibodies, these specifically target & destroy T lymphocytes by binding to their surface CD3 Ag
  • FK-506 (-) lymphokine production
  • cyclosporine A (-) T cell lymphokine production
124
Q

renal allograft recipient is given anti-CD3 (a monoclonal antibody) to treat rejection episode. Possible outcome

A
  • type III hypersensitivity
  • the production of anti-mouse antibodies
  • suppression of the rejection episode
  • rejection of the allograft

GSSE (15 decks)

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