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Mechanism of Disease > Immunopathology and Hypersensitivity > Flashcards

Immunopathology and Hypersensitivity Flashcards

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1
Q

What are the general principles of the immune response?

A
  • Multilayer defense
  • Pathogen recognition
  • Effective inter-cellular communication
  • Self-regulation
  • Limitation of host damage
  • Adaptive responses to changing pathogen
  • Multiple mechanisms of pathogen clearance
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2
Q

What are the innate and adaptive branches of the immune system?

A 
Innate= Cellular (phagocytes & natural killer), PRR, barrier and chemical mechanisms
Adaptive= Cellular, humoral
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3
Q

What are pattern recognition receptors?

A
  • Antigen recognition receptors of innate system
  • Common recognition of PAMPs & DAMPs
  • 2 groups: cell surface & intracellular receptors
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4
Q

Name the major components of the innate immune system

A
  • Pattern recognition receptors
  • Antimicrobial peptides
  • Cells
  • Complement components
  • Cytokines
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5
Q

Describe fluid-phase recognition molecules

A
  • C type Lectin family= Collectins (surfactant protein A&D)
  • Recognition of microbial complex carbohydrates
  • Bind via CRDs
  • Neutralisation of pathogens
  • recruitment of adaptive response
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6
Q

What is the source and target of TNF?

A

Source: macrophages & T-lymphocytes

Target: Hepatocytes, neutrophils, inc inflammation & activation

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7
Q

What is the source and target of IL6?

A

Source: macrophages, T-lymphocytes, endothelia

Target: inc B-lymphocyte proliferation

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8
Q

What cell types of the innate immune system are there?

A
  • Macrophages
  • Natural killer
  • Eosinophil & neutrophil
  • Plasmacytoid & myeloid dendritic
  • Mast cells & basophils
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9
Q

What is the mechanism for antigen presentation?

A
  • Antigens internalised
  • Broken down to peptides
  • Associated with newly synthesised class 2 molecule and brought to surface
  • Foreign peptides recognised by T-helper which are activated
  • Produce cytokines needed by B&T cells
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10
Q

What does HLA stand for? What is its other name? What is ir?

A
  • Human leucocyte antigens
  • Histocompatability antigens
  • glycoproteins on cell surface making them unique
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11
Q

What are functions of Class 1&2 MHC proteins?

A

Class1: present peptides to cytotoxic T cells
Class2: present peptides to helper T cells

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12
Q

What is the function of

B-lymphocytes?

A

Potential to secrete antibodies: humoral immunity

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13
Q

What is the function of killer/cytotoxic T cells?

A

Kill- cellular immunity

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14
Q

What is the function of helper T cells?

A
  • Secrete growth factors (cytokines) which control immune response
  • Help B&T lymphocytes
  • Target of HIV
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15
Q

What is the function of suppressor T lymphocytes?

A

Dampen down immune response

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16
Q

How can binding of antibodies to antigens inactivate the antigens?

Study These Flashcards
A

-Neutralisation (blocks viral binding sites& coats bacteria)
-Agglutination of microbes (clumping together)
-Precipitation of dissolved antigens
ALL ENHANCE PHAGOCYTOSIS
Activation of complement system (leads to cell lysis)

17
Q

How does cell lysis occur?

Study These Flashcards
A

1) Cytotoxic T cell binds to infected cell
2) Perforin makes holes in infected cell’s membrane, enzymes enter
3) Infected cell destroyed

18
Q

Define immunosuppression and immunodeficiency

Study These Flashcards
A

IS= Natural/artificial process which turns off the immune response
ID: A result of IS and the lack of an efficient immune system, susceptibility to infections

19
Q

When is immunosuppression seen?

Study These Flashcards
A
  • Inhibit transplant rejection
  • Autoimmune diseases
  • Lymphoproliferative diseases
20
Q

Define hypersensitivity

Study These Flashcards
A

Undesirable/damaging and sometimes fatal reactions produced by immune system in a pre-sensitized host.

21
Q

What types of hypersensitivity are there?

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A

I) IgE Mediated
II) Cytotoxic reaction
III) Immune complex reaction
IV) Cell mediated reaction (DTH)

22
Q

Describe a form of type I hypersensitivity

Study These Flashcards
A
  • Anaphylactic (severe reaction)
  • Mast cell & basophil degranulation
  • Release of preformed & de novo inflammatory mediators (histamine) & lipid mediators (leukotrienes)
  • Pollen, bee venom, animal dander, hayfever, allergic asthma
23
Q

What are the clinical features of anaphylaxis?

Study These Flashcards
A
  • Fast onset
  • Weal & flare
  • Sometimes late 2nd phase
  • contraction of s.muscle
  • Dilatation of blood vessels
  • Mucous glands
24
Q

Describe immunoglobulin E

Study These Flashcards
A
  • Produced by plasma cells from class-switched B cells
  • Under control of IL-4 & CD40L
  • Extremely low serum levels
  • High affinity receptor for IgE on mast cells & basophils
  • Stable binding over long periods
25
What happens in the early phase response of a reaction?
- Mast cell FCER1 presents at high density - cross-linking by allergen leads to activation of mast cells - degranulation & release of preformed mediators - synthesis of lipid mediators
26
Name some preformed mediators
- Histamine= s.muscle contraction, inc vascular permeability, stimulation of irritant nerve response - Kallikrein= activates bradykinin - Tryptase
27
What are lipid mediators?
- Arachidonic acid derivatives - Phospholipase A2 broken down to arachidonic acid - Finally forms leukotrienes - And Prostaglandins
28
What happens in the late phase response of a reaction?
- Basophils= similar properties to mast cells but over longer time scale - Eosinophils= Granules contain cytotoxic proteins, attracted to site of inflammation by chemokines, release contents of granules in tissue - major source of tissue damage in allergic response - T cell= in both early&late response, cytokine production by activated T cells needed for ongoing response - Cytokine-driven activity major source of pathogenesis in allergic reaction
29
Name some examples of allergic diseases
- Asthma - Rhinitis - Dermatitis - Food allergy
30
Describe type II hypersensitivity
- Antibody mediated cytotoxic - Binding of antibody to antigen causes activation of complement cascade=cell lysis - Aggregation of Fc portions of immunoglobulin binding to FcRs = opsonisation/phagocytosis/destruction
31
What is type II hypersensitivity initiated by?
- initiated by IgM (sometimes IgG) - IgM most efficient since pentavalent - IgG requires multiple binding
32
What is effected in type II hypersensitivity?
- Haematopoietic cells - Neutrophils - Platelets - Blood group incompatbility - Autoimmune haemolytic anaemias
33
Describe type III hypersensitivity
- IgG + Ag= AgAb complex - Complement activation leads to generation of activated complement fragments - C5a= attractant for neutrophils - C3b= opsonin - Attempted phagocytosis of complexes leads to release of enzymes& O2 radicals - Results in tissue damage
34
Name some diseases from type III hypersensitivity, their route into the body and the site of immune complex deposition
-Vasculitis-Blood vessel walls Nephritis- Renal glomeruli Arthritis-joint space ALL INTRAVENOUS ROUTE Subcutaneous route- arthus reaction- perivascular area Inhaled route- Farmer's lung- alveolar/capillary interface
35
Give some examples of other antibody-mediated immunopathology
- Inactivation= DIRECT: Intrinsic factor in B12 deficiency - Inactivation= INDIRECT: binding to hormone results in clearance of AgAb complex - Receptor blockade= Myasthenia Gravis
36
Describe type IV hypersensitivity
- T cell mediated (CD4+/MHC class II) - Delayed (tuberculin skin reaction) - Age-specific T cell release cytokines- recruitment of macrophages - Activated macrophages cause tissue damage - Requires previous exposure to antigen - Hapten(allergen) presented to skin causes reaction in langerhan cells
37
Give examples of other cell-mediated immunopathology
- Tcell mediated cytotoxicity - CD8+/MHC class I - Contact dermatitis (combination of DTH& cytotoxic reaction) - Nickel/poison ivy can act as hapten with epidermal proteins
38
What are granulomatous reactions?
- Focal collections of inflammatory cells in tissue (macrophages, epithelioid cells, giant cells & lymphocytes) - Th1- type T cells secrete IL2& IFNy - _IL-12 release by macrophages critical in initial response
39
Name some granulomatous diseases
- Infections: mycobacterial= TB, atypical mycobacteria, Leprosy - unknown = Sarcoidosis, Wegener's Granulomatosis, Crohn's

Mechanism of Disease (18 decks)

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