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Medicine year 2 semester 1 > Case 17- TB and lymphoid organs > Flashcards

Case 17- TB and lymphoid organs Flashcards

1
Q

TB and HIV

A

It is the leading cause of death among people with HIV, it causes one in three AIDs related deaths

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2
Q

Causative agent of TB

A

TB is caused by bacteria of the Mycobacterium tuberculosis complex- mainly Mycobacterium tuberculosis, rarely Mycobacterium bovis.

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3
Q

TB transmission

A

Through the respiratory route from those with infectious active pulmonary TB coughs

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4
Q

Classifying the Mycobacterium tuberculosis complex

A

Aerobic rods, occasionally form branched filaments. The gram stain does not work, the acid fast staining process is used and is often referred to as acid fast bacteria, stain gives them a deep purple colour. Mycobacteria have a lipid rich cell wall (major pathogenicity factor).

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5
Q

Epidemiology of TB

A

1) V high rates in subsaharan Africa, South East Asia
2) HIV with TB is most common in sub-saharan Africa
3) UK is a low incidence country
4) There is a slow decrease in TB cases and overall deaths worldwide
5) TB is one of the top 10 causes of death worldwide, multi-drug resistant TB has started to develop

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6
Q

What is TB associated with in England

A

People born outside the UK account for 72% of TB notifications, TB is associated with deprivation.

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7
Q

TB- what happens after primary exposure

A

After exposure to the primary case of TB about 70% of people will have no infection. Of those infected over 90% will have immune activation and granuloma formation and then latency. In immunocompromised people (<10%) there will be reactivation of TB leading to the active disease. Its far greater in those with HIV. There will be failure of immune activation and this leads to the primary disease (active disease).

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8
Q

Clinical features of TB- the 4 different types

A
  • Active pulmonary TB- the most common presentation
  • Active extrapulmonary TB- presents with symptoms specific to the site involved (CNS/ Lymph nodes/ Bones and joints/ Pericardium/ GU). Can get spinal TB, infection of the lymph nodes and granuloma formation.
  • Latent TB- occurs when the Mycobacterium bacteria remains dormant and is asymptomatic, reactivation in about 10% of cases
  • Multidrug resistant TB- refers to a strain of TB that is resistant to two first line drugs
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9
Q

Risk factors for TB

A
  • Being born in high prevalence areas
  • Close contact with TB
  • Previously (especially incomplete) treatment for TB
  • Comorbidities
  • Social risk factors
  • Alcohol or drug misuse
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10
Q

When should you suspect TB

A

In patients who have a high risk of developing TB and have general symptoms of weight loss, fever, night sweats, anorexia and malaise

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11
Q

When should you consider pulmonary involvement in TB

A

Once other things have been rules out- persistent productive cough, breathlessness and haemoptysis

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12
Q

Pulmonary TB

A

Causes destruction of lung tissue, there will be abnormal x-rays with considerable scarring. There can be granuloma formation in the lungs

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13
Q

Latent TB

A
  • Initial stage of TB infection causes the innate immune response followed by the adaptive immune response.
  • Recruitment of T cells, B cells, activated macrophages and other leukocytes leads to the establishment of granulomas, less likely to happen in HIV.
  • Granulomas are cellular aggregates which are pathologic hallmarks of tuberculosis thought necessary for containment of infection. It restrains and contains the infection
  • Most infected individuals will remain in the latent state of infection
  • <10% will progress to active disease when granulomas have eroded into the airway. Transmissive granuloma
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14
Q

Miliary tuberculosis

A

Very rare, characterised by wide dissemination. There will be tiny spots on the chest x-ray, can disseminate to other tissues, fatal if untreated

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15
Q

TB clinical features- latent and active

A
  • Latent- asymptomatic, non-infective, positive skin test or blood test for indicating TB infection, normal chest x-ray and a negative sputum smear, needs treatment for latent TB
  • Active- symptomatic, infective, positive skin test or blood test for indicating TB infection, abnormal chest x-ray or positive sputum smear or culture, needs treatment for active TB disease
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16
Q

Treatment for active TB

A

Active antibiotic drug treatment with combination regimens:
• Usually 6 months of isoniazid (with pyridoxine) and rifampicin
• Supplemented in the first 2 months with pyrazinamide and ethambutol
You tend to stop treatment when there is a negative smear or culture

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17
Q

Treatment for latent TB

A
  • 3 months with isoniazid (with pyridoxine) and rifampicin, or
  • 6 months of isoniazid (with pyridoxine)
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18
Q

Completing TB treatment

A 
15% of patients do not complete their course of treatment. Patients should complete treatment to reduce the risk of:
• Drug resistant TB
• Onward transmission
• Relapse of disease
• Dying
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19
Q

Problems of TB treatment (resistance)

A
  • Mono-resistance= resistance to one first line anti-TB drug only
  • Poly-resistance= resistance to more than one first line anti-TB drug, other than both isoniazid and rifampicin
  • Multidrug resistance (MDR)= resistance to at least both isoniazid and rifampicin
  • Extensive drug resistance (XDR)= resistance to any fluoroquinolone and at least one of the three second line injectable in addition to multidrug resistance.
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20
Q

Issues with MDR TB

A

Limited and expensive treatment options, poor availability of second line treatment. Adverse side effects

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21
Q

Prevention of TB

A
  • Vaccination
  • Contact tracing
  • Surveillance and monitoring
  • Make sure treatment is complied with to prevent drug resistant forms
  • Screening for TB
  • Workforce availability
  • Quality diagnostics
22
Q

TB vaccination

A

BCG vaccination, it is 70-80% effective against the most severe forms of TB such as TB meningitis and milliary TB. It’s the least effective against pulmonary TB (50%). Only given in areas of high prevalence. It was on the schedule from 1953 to 2005 for 10-14 year olds. Its given at birth in countries with high prevailence.

23
Q

Latent TB- brief

A

Mycobacterium remains dormant and asymptomatic. Not infective but positive on blood tests, treat for latent TB to prevent from becoming active

24
Q

The primary lymphoid organs

A

The bone marrow and the thymus

25
Q

First step of B and T cell development

A

Production of a common HSC, a lymphoid cell precursor. In the bone marrow the lymphoid progenitors become committed to either a B or T cell

26
Q

Where does B cell development take place

A

The bone marrow

27
Q

Stromal stem cells in the bone marrow

A

Stromal stem cells in the bone marrow i.e. skeletal or mesenchymal stem cells provide the suitable micro environment for B cell development. Allows for functional gene rearrangement which lead to functional B cell receptor. The stem cells provide the cytokine IL-7 which is essential for B cell development, when it binds to the B cell it initiates a signalling cascade. The B cells are very close to the stromal stem cells

28
Q

Where does T cell development take place

A

1) In the bone marrow there is development of the T cell lineage from the HSC
2) Immature T cells migrate to the thymus
3) Functional gene rearrangement leads to development of the TCR

29
Q

Thymus

A

A multi-lobed organ with an outer capsule. Has two distinct layers the outer cortex and the inner medulla, each has a role. The Thymus sequesters (degrades) with age, people get more infections with age.

30
Q

Hassall’s corpuscle

A

Linked to autoimmune disease

31
Q

T cell development in different areas of the Thymus

A
  • Progenitor T cells are derived from the bone marrow
  • Initially they are CD4-ve and CD8-ve (double negative thymocyte)
  • T cell precursors enter the sub-capsular cortical areas
  • They encounter networks of cortical epithelial cells (the thymic stroma)
  • A functional TCR is produced
  • CD4+ and CD8+ double positive
  • Positive selection for functional TCR
  • Move into the medulla where they become CD4 or CD8 cells, if they autoreact they undergo apoptosis. T cells then move to the periphery
  • If there is weak binding for self cells then they become T-regulatory cells
32
Q

What happens in the cortex of the Thymus

A
  • Double negative T cells fate selection pathway- become either αβ T cells (90-95%) γδ (gamma delta) T cells (non-MHC restricted, Lipid, non-protein, may be important in epithelia boundaries e.g. gut).
  • TCR gene recombination- sequential beta-chain and alpha-chain rearrangement
  • Expression of CD4 and CD8- double positive
33
Q

What happens in the Medulla of the Thymus

A

Negative selection, conversion to single negative CD4 or CD8

34
Q

Selection in the thymus for functional TCR’s

A
  • β-selection: occurs after β-chain rearrangement (cortex), if you don’t have a beta chain you wont proceed
  • If survive β-selection, upregulate CD4/8 → Double positive
  • Double positive B cell undergo α-chain rearrangement
  • Then positive selection (cortex) for interaction with self MHC
  • Then negative selection in medulla for interaction with self peptides on MHC
  • Switch to Single positive CD4 or CD8
35
Q

What happens to T cells as you age

A

Your memory T cells will remain but your naive T cells disease, this is because thymic output decreases with age. Means you have a less robust response with new infections

36
Q

Secondary lymphoid organs

A

Main sites of immune activation against protein antigens (T cell dependent). The spleen is also important in B cell development i.e. follicular B cells and marginal zone B cells. Certain follicles are populated with follicular B cells, used in the activation and production of antibodies and interaction with T cells.

37
Q

Types of secondary lymphoid organs

A

Lymph node, Tonsils, Adenoid, Lymphoid aggregates, Spleen, Peyer’s patch, Appendix

38
Q

The Lymph node

A

Main drainage/ filter for lymph. For antigens from peripheral tissue. Highly vascularised, interacts with the blood circulation which provides the lymph nodes with the B and T cells. Contains lots of follicular B cells and high endothelial venules which are needed when communicating with the blood system. Filters antigens which may be presented on dendritic cells

39
Q

The lymph node- germinal centre and mantle zone

A

The lymph node structure is a germinal centre surrounded by a mantle zone. Mantle zone is occupied by T cells and inactivated B cells. The germinal centre consists of activated B cells. There is a clear division between the B and T cells within the lymph node

40
Q

Structure of lymph node

A

1) Follicle (B cells)
2) Paracortex (T cell zone)- part of the cortex, near the centre
3) Cortex
4) Medulla
5) Capsule
6) Trabecula

41
Q

Lymph node paracortex

A

Contains High Endothelial Venules (HEV) which allow T cells to enter the Lymph node directly from the blood. They also enter via the afferent lymph vessels. The activated T cells leave via the efferent lymph vessels.

42
Q

How T and B cells move through the lymph node

A
  • Interstitial fluid drains into the lymph node via the afferent lymphatic vessels
  • They come into contact with the B and T cell lymphocytes.
  • T cells enter via the HEV into the paracortex
  • The T cells then drain into the efferent lymph node and can make their way back to circulation through the thoracic duct
  • Naïve B cells circulate through the lymph nodes and find antigens presented on dendritic cells.
43
Q

Spleen

A
  • Filtration of blood, removes old red blood cells
  • Main protection against blood born pathogens
  • Contain follicles populated with follicular B cells, these B cells are T cell dependent
  • Follicles have a marginal zone- contains marginal zone B cells which are T cell independent, so may be used against capsulated bacteria
  • Germinal centre- mostly B cells
44
Q

Structure of Spleen

A
  • Highly vascularised organ
  • Like lymph node it is encapsulated
  • Contains red pulp (70%)- a reservoir for RBC’s, platelets and macrophages
  • White pulp- mainly lymphocytes (B and T cells), separated from red pulp by marginal zone. The marginal zone traps particulate matter so only small cells get through, acts like a filter. Antigenic material is presented to the lymphocyte in the white pulp
  • Trabecular- helps physically support the spleen
  • Periarterial lymphoid sheath (PALS)- portion of the white pulp, populated mostly by T cells and surrounds the central artery (separates it from the germinal centre). The PALS-T cell is presented with blood borne antigens by dendritic cells or directly.
  • The germinal centre is surrounded by the marginal zone and the mantle zone.
45
Q

Movement of blood through the spleen

A

Moves through the trabecular arteries and then into smaller arteries. The Antigens and dendritic cells then diffuse out into the PALS, this activates the T cells which activate the B cells within the germinal centre. The B and T cells then re-enter the general circulation though the Penicillar arterioles.

46
Q

Mucosal associated Lymphatic tissue (MALT)

A

Unencapsulated or partially capsulated, the organisation is more diffuse compared to lymph node or spleen. Role is to encounter antigens passing through the mucosal epithelium i.e. GALT.

47
Q

Tonsils (MALT)- Waldeyer’s tonsilar ring

A

Adenoid tonsil, two tubal tonsils, two palatine tonsils, and Lingual tonsils. It’s a more organised MALT.

48
Q

Diffuse MALT

A

Peyer’s patch, type of GALT. Contains small gaps which are where the mast cells are, they pick up antigens and pass them into the T cells.

49
Q

Germinal centre B cells

A

In the Germinal centre you get proliferation and differentiation of B cells with the production of antibodies. You get somatic hypermutation (select for better antibodies) and clonal expansion. Antibodies and memory cells are produced. When the B cells first encounter an antigen in the B cell follicle you get IgM production, its only in the germinal centre that you get class switching and IgG production. IgM is the primary response and IgG is the secondary response

50
Q

Germinal centre- light and dark zone

A
  • Activation of B cells and migration into the germinal centre
  • B cell proliferation (dark zone) and somatic hypermutation (light zone)
  • Selection of high affinity B cells, isotype switching (light zone)
  • Exit of high affinity antibody secreting cells and memory B cells

Medicine year 2 semester 1 (53 decks)

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