L5&6- Immunopathology Flashcards

1
Q

general overview of Innate immune system

A

Innate:
-Barrier and chemical mechanisms

  • PRR (Pattern recognition receptor) - proteins expressed by cells to identify two classes of molecular patterns: 1) pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and 2) damage-associated (DAMPs), which are associated with cell components that are released during cell damage or death.
  • Phagocytes, natural killer cells
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2
Q

General overview of adaptive immune system

A

Humoral

Cellular

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3
Q

Pattern recognition receptors

A

Antigen recognition receptor in innate system

Common theme is recognition of Pathogen-associated Molecular Patterns (PAMPs) but also Danger Associated Molecular Patterns (DAMP’s)

2 groups

  • Cell surface (transmembrane) and intracellular receptors – TLRs, NLRs, RLR’s and CLR’s
  • Fluid-phase soluble molecules
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4
Q

FLUID-PHASE RECOGNITION MOLECULES

A

C-TYPE LECTIN FAMILY

  • COLLECTINS
    • Mannan-binding Lectin
    • Surfactant Protein A & D

Role in neutralisation of pathogen
Role in recruitment of adaptive response

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5
Q

Steps of Classical Pathway

A

Antigen+Antibody Complex –> c1, c4, c2 —> C3 convertase

From C3 convertase can go 3 ways:
1) c3a, c5a –> peptide mediators of inflammation, phagocyte recruitment

2) c3b –> binds to complement receptor on phagocyte —>opsonisation of pathogens —> removal of immune complexes
3) c3b —> c5b, c6, c7 ,c8 ,c9 —> Membrane attack complex, lysis of certain pathogens and cell

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6
Q

What is opsonization

A

An immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte .

The process of opsonization is a means of identifying the invading particle to the phagocyte

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7
Q

Function of macrophages

A

Phagocytose and kill bacteria; produce antimicrobial peptides; bind (LPS); produce inflammatory cytokines

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8
Q

Function of Plasmacytoid dendritic cells (DCs)

A

Produce large amounts of interferon- (IFN-) which has antitumor and antiviral activity, and are found in T cell zones of lymphoid organs; they circulate in blood.

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9
Q

Function of Myeloid dendritic cells

A

Interstitial DCs are strong producers of IL-12 and IL-10

Langerhans DCs are strong producers of IL-12

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10
Q

function of Natural killer (NK)

A

Kill foreign and host cells that have low levels of MHC+ self peptides. Express NK receptors that inhibit NK function in the presence of high expression of self-MHC

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11
Q

Function of NK-T cells

A

Lymphocytes with both T cell and NK surface markers that recognize lipid antigens of intracellular bacteria such as M. tuberculosis by CD1 molecules and kill host cells infected with intracellular bacteria.

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12
Q

Function of Neutrophils

A

Phagocytose and kill bacteria, produce antimicrobial peptides

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13
Q

Function of Mast cells and basophils

A

Release TNF-, IL-6, IFN- in response to a variety of bacterial PAMPs

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14
Q

Function of Epithelial cells

A

Produce anti-microbial peptides; tissue specific epithelia produce mediator of local innate immunity, e.g. lung epithelial cells produce surfactant proteins (proteins within the collectin family) that bind and promote clearance of lung invading microbes

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15
Q

ADAPTIVE IMMUNE RESPONSE

A

Evolution in response to changing pathogen structures

In response to infection this lymphocyte undergoes CLONAL expansion

High degree of specificity

VDJ recombination enables multiple immunoglobulin structures

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16
Q

Mechanism of antigen presentation

A

Antigens are internalised

Broken down to peptides

Peptides associate with newly synthesised Class 2 molecules and are brought to the cell surface.

If the peptides are foreign they are recognised by helper T cells which are then activated.

Helper T cells produce cytokines needed by B cells, T cells , etc.

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17
Q

FUNCTIONS OF CLASS 1 MHC

A

The function of these proteins is to present antigenic peptides to T cells- T cells only see antigen in association with MHC Proteins.

MHC class 1 proteins present peptides to cytotoxic T cells

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18
Q

FUNCTIONS OF CLASS 2 MHC

A

The function of these proteins is to present antigenic peptides to T cells- T cells only see antigen in association with MHC Proteins.

MHC Class 2 proteins present peptides to helper T cells

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19
Q

Lymphocytes-function: B lymphocytes

A

develop potential to secrete antibodies: humoral immunity

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20
Q

Lymphocytes-function: T lymphocytes

A

Killer or cytotoxic T lymphocytes are able to kill. Cellular immunity

Helper T lymphocytes secrete growth factors (cytokines) which control immune response: Help B lymphocytes and T lymphocytes (Helper T cells are target of HIV)

Suppressor T lymphocytes may damp down immune response

21
Q

Binding of antibodies to antigens inactivates the antigens by…?

A

Neutralization (blocks binding sites, coats bacteria)

Agglutination of microbes

—> Phagocytosis

Activation of complement —> cell lysis

22
Q

What happens when cytotoxic t cell binds to foreign antigen?

A

Recognises non self antigen –> binds to infected cell –> Releases Perforin (hole forming) enzyme that can promote apoptosis –> infected cell destroyed

23
Q

IL2

A

T cell growth factor (and IL 15)

24
Q

Do we need to know the different cytokines for adaptive and innate immunity?

A

I don’t know? :s

25
Q

Immunosuppression

A

A natural or artificial process which turns off the immune response, partially or fully, accidentally or on purpose

Uses:
Transplant rejection
Autoimmune diseases
Lymphoproliferative diseases

26
Q

Immunodeficiency

A

the lack of an efficient immune system-susceptibility to infections

27
Q

What pathogen can affect PRR (e.g TLR)?

A

Pneumococcus

HSV

28
Q

What pathogen can affect the Complement pathway?

A

Meningococcus

29
Q

What disorder can affect white blood cells or cause the absence of them?

A

SCID

Opportunistic infections

30
Q

What would affect release of cytokines?

A

Mycobacterium

31
Q

What type of infections what result in poor antibody response?

A

Recurrent Sino-pulmonary infections

32
Q

Hypersensitivity

A

Undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system (directed against innocuous antigens) in a pre-sensitized (immune) host

33
Q

HYPERSENSITIVITY TYPES

A

TYPES I - IV

I - IgE MEDIATED REACTION

II - CYTOTOXIC REACTION

III - IMMUNE COMPLEX REACTION

IV - CELL MEDIATED REACTION (DTH)

34
Q

Type I (anaphylactic) Hypersensitvity

A

Immunopathogenesis:
IgE Ab mediated mast cell and basophil degranulation- release of preformed and inflammatory mediators

Clinical features:
Fast onset (15-30 min)
Weal and flare
Early phase and late phase

Common antigens:
Pollen, bee venom, animal dander

Associated diseases:
Hay fever, allergic asthma

35
Q

IMMUNOGLOBULIN E

A

Produced by plasma cells from class-switched B cells under the control of IL-4 and CD40L - CD40 interaction

Extremely low serum levels BUT

High affinity receptor for IgE (FceRI) on mast cells and basophils
Permits stable binding over long periods

36
Q

PRE-FORMED MEDIATORS

A

HISTAMINE
Stimulation of irritant nerve receptors
Smooth muscle contraction
Increase in vascular permeability

KALLIKREIN
Activates bradykinin - similar actions to histamine

37
Q

LIPID MEDIATORS

A

ARACHIDONIC ACID DERIVATIVES

Arachidonic acid –> (Lipoxygenase) –>Leukotrienes

Arachidonic acid–> (cycloxygenase) –>Prostaglandins (e.g:PROSTACYLINE, THROMBOXANE )

38
Q

Late phase responses Type 1 hypersensitivity

A

BASOPHILS
Similar properties to mast cells over longer time scale

EOSINOPHILS
GRANULES contain cytotoxic proteins (e.g. Eosinophil Cationic Protein)
Attracted to sites of allergic inflammation by CHEMOKINES (e.g. Eotaxin 1/2)

39
Q

Late phase responses Type 2 hypersensitivity

A

T CELL RESPONSES
-Involved in both EARLY and LATE response to allergen

-Cytokine production by activated T cells critical in ongoing response

CYTOKINE-DRIVEN ACTIVITY is the major source of PATHOGENESIS in allergic responses

40
Q

EXAMPLES OF ALLERGIC DISEASES

A

ASTHMA

RHINITIS

DERMATITIS

FOOD ALLERGY

41
Q

What happens in HYPERSENSITIVITY - TYPE II

A

Antibody-mediated cytotoxic reactions

Binding of antibody to target antigen on cell membrane results in:-
-Activation of the complement cascade resulting in cell lysis

-Aggregation of Fc portions of immunoglobulin/C3b with binding to FcRs/C3bR resulting in opsonisation, phagocytosis & destruction

42
Q

Causes of HYPSERSENSITIVITY - TYPE II

A

Initiated by IgM or complement-binding IgG
IgM&raquo_space; IgG1 & IgG3

IgM most efficient since pentavalent
IgG requires multiple binding

Cells usually affected are haematopoietic cells e.g:

  • Blood group incompatibility
  • Autoimmune haemolytic anaemias
  • Affecting neutrophils
  • Affecting platelets
43
Q

HYPERSENSITIVITY - TYPE III

A

IMMUNE COMPLEX REACTIONS
1. IgG + Ag = AgAb complex

  1. FcR in complex bind C1q
  2. Complement activation leads to generation of activated
    complement fragments

4a. C5a - attractant for neutrophils
4b. C3b - Opsonin

  1. Attempted phagocytosis of complexes - release of enzymes, oxygen radicals
  2. Consequence is tissue damage
44
Q

Examples of HYPERSENSITIVITY - TYPE III

A

Vasculitis
Nephritis
Arthritis
Farmer’s lungs

45
Q

OTHER ANTIBODY-MEDIATED IMMUNOPATHOLOGY

A

Inactivation:

  • Direct
    e. g. to Intrinsic factor - B12 deficiency

-Indirect
binding to e.g. hormone results in clearance of AgAb complex

  • Receptor blockade
    e. g. To AChR in Myasthenia Gravis
46
Q

HYPERSENSITIVITY - TYPE IV

A

T cell mediated - CD4+ cells (MHC class II)

  • Delayed type e.g. Tuberculin skin reaction
  • Initially perivascular infiltration of lymphocytes & monocytes
  • LANGERHAN’S cells present neo-antigen to T cells
  • Ag-specific T cells release cytokines - recruitment of macrophages (non Ag-specific)
  • Activated macrophages cause tissue damage
  • Requires previous exposure to antigen
47
Q

OTHER CELL-MEDIATED IMMUNOPATHOLOGY

A

T cell-mediated cytotoxicity
CD8+ T cells (MHC Class I)

Contact dermatitis
e.g. Nickel, poison Ivy
Combination of DTH and cytotoxic reaction
Nickel acts as hapten with epidermal proteins
Antigen presentation by APC
Keratinocytes may present to CTL precursors

48
Q

GRANULOMATOUS REACTIONS

A

Granulomas:

  • Focal collections of inflammatory cells in tissues
    • Macrophages
    • Epithelioid cells (phagocytic cells containing foreign material)
    • Giant cells
    • Lymphocytes

T cells are Th1-type - secrete IL2 & IFNg
Release of IL-12 by macrophages critical in initiation of response

49
Q

GRANULOMATOUS DISEASES

A

Infections:

  • Mycobacterial
    • Tuberculosis
    • Atypical mycobacteria
    • Leprosy
      • Tuberculoid - Th1 - Protective
      • Lepromatous Th2 - Non-protective

Unknown aetiology:

  • Sarcoidosis
  • Wegener’s Granulomatosis
  • Crohn’s disease