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Immunopathology > Lecture 10 > Flashcards

Lecture 10 Flashcards

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1
Q

What is a pathogen?

A

An agent that causes or generated disease
- Micro-organisms
- Parasites
- Foreign particles/substances

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2
Q

What are micro-organism?

A

Bacteria, virus, fungi, etc.

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3
Q

What are examples of parasites?

A

Dust mites, nematodes etc

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4
Q

What is an antigen?

A

A substance that has the ability to provoke an immune response
- Foreign molecule
- Nonself/Intruders

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5
Q

What are the primary lymphoid organs?

A
  • Bone marrow: Site of hematopoiesis and B-cell mutation
  • Thymus: Site of T cell maturation
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5
Q

What are the 4 components of the immune system?

A
  1. Primary Lymphoid Organs
  2. Secondary Lymphoid Organs
  3. Cellular Components
  4. Molecular Components
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6
Q

What are the secondary lymphoid organs?

A
  • Lymph nodes: Filters lymph and facilitates immune response
  • Spleen: Filters blood and responds to systemic infections
  • Mucosa-associated lymphoid tissue (MALT): Protects mucosal surface
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7
Q

What are cellular components of the immune system?

A
  • WBCs: Neutrophils, lymphocytes, monocytes, eosinophils, basophils and NK cells
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8
Q

First Line defencse-surface barrier

A

Respiratory Tract:
- Nose hairs
- Mucus
- CIlia

Gastrointestinal Tract:
- pH
- Mucus
- Enzymes

Skin:
- RNases, DNases
- Fatts acids
- Keratinized epithelium

Urogenital Tract:
- pH
- Mucus
- Fluid pressure

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9
Q

Second Line defence: Innate Immunity

A
  • Non-specific protection against foreign materials or cells
  • Present at birth and does not improve on repeated contact
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10
Q

What does the Second Line defence: Innate Immunity include?

A
  • Phagocytes
  • NK cells
  • Inflammation
  • Antimicrobial protein
  • Fever
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11
Q

What is the key role of phagocytes?

A
  • Detection
  • Phagocytosis
  • Elimination of foreign substances
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12
Q

How do phagocytes communicate with other defence cells?

A

Via cytokines

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13
Q

How do phagocytes attract other immune cells?

A

Via chemokines (type of cytokine causing chemotaxis)

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14
Q

Where are phagocytes located?

A

Some are fixed in tissue:
- Kuppfer cells in the liver

Some travel (free):
- Monocytes/macrophages
- Denrocytes
- Neutrophils

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15
Q
A
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16
Q

What are the 5 steps of phagocytosis?

A
  1. Phagocyte adheres to pathogen/debris
  2. Phagocyte forms pseudopods that eventually engluf particles forming a phagosome
  3. Lysosome fuses with the phagocytic vesicle
  4. Lysosomal enzymes digests the particle, leaving residual body
  5. Exocytosis of vesicle removed indigestable and residual material
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16
Q

Functions of the complement system

A
  1. Lysis of target cells
  2. Facilitate Ag clearance
  3. Generate an inflammatory response
  4. Clearance of immune complexes
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16
Q

What are natural killer cells?

A

Large granular lymphocytes responsible for recognizing and destroying abnormal cells when they appear in peripheral tissues

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17
Q

How is the complement system activated?

A

Involves a highly regulated enzymatic cascade

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17
Q

What is the complement system?

A

A group of around 30 glycoproteins present in plasma/serum and on cell membranes that normally remain in an inactive state
- Innate immunity

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17
Q

REVISE ACUTE INFLAMMATION AND TYPES OF LEUKOCYTES

A
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18
Q

Lectin Complement Pathway

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A

Involves Mannose-binding lectin (MBL)
- Lectins are proteins that can bind to carbohydrate molecules present on pathogens such as:
*Salmonella
*Candida albicans
*Influenza A
*Leishmania

18
Q

How can a complement cascade be activated?

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A
  • Classical pathway
  • Alternate pathway
  • Lectin pathway

Culminate in the formation of a membrane attack complex (MAC) and Antigen clearance

18
Alternative complement pathway
- Initiated by cy cell surface constituents forein to the host - C3 spontaneously hydrolyses to C3a and C3b - Free C3b can bind to foreing cell walls, viruses and host cells
19
What is the classical Complement Pathway
Initiated by formation of soluble Ag-Ab complexes or binding of Ab to Ag on suitable target - Only activated by IgM, IgG1, IgG2 and IgG3
20
How does fever occur in immune defence?
When leukocytes and macrophages are exposed to pathogens, theu release pyrogens - Pyrogens act on bodys thermostat * Cluster of neurons in hypothalamus increase temp
21
Antimicrobial proteins
Enhance the innate defences by attacking microorganisms directly or by hindering their ability to reproduce - Interferons - Complement proteins
22
Interferon alpha
Produced by cells infected with viruses, it attracts and stimulates NK cells and enhances resistance to viral infection
23
Interferon beta
Secreted by fibroblasts and slows inflammation in a damaged area
24
Interferon gamma
Secreted by t cells and NK cells and stimulates macrophage activity
25
How do T cells see antigens?
T cells only recognise Ag when presented in the context of self major Histocompatibility Complex (MHC)
26
Antigen Presenting Cell
- Different cell types - Mediated the cellular immune response - Present antigen to cells that deal with antigens Examples: - Dendritic cells - macrophages - B lymphocytes
27
What is the Major Histocompatibility Complex (MHC)
A group of genes that encode cell surface proteins essential for the immune system to recognize and respond to foreign antigens
28
Where is MHC located?
In humans it is referred to as Human Leukocyte Antigen (HLA) and is located on chromosome 6
29
What is the function of MHC?
presents antigenic peptides to T lymphocytes, initiating an adaptive immune response
30
MHC Class I
- Composed of one alpha chain and one beta-2 microglobulin - Alpha chain has 3 domains (alpha 1, alpha 2, alpha 3) - Peptide-binding groove is located between alpha 1and alpha 2
31
MHC Class II
- Composed of two chains (alpha and beta) each with two domains (alpha 1, alpha 2, beta 1, beta 2) - Peptide-binding groove is located between alpha 1 and beta 1
32
Where is MHC Class I found?
Surface of all nucleated cells
33
What antigens does MHC Class I present?
Endogenous antigens (e.g. viral or intracellular proteins)
34
What cells is MHC Class I recognised by?
CD8 and Cytotoxic T cells
35
What is the pathway of MHC Class I?
- Pathogens degraded by proteasome - Peptides transported to ER via TAP - Peptides are loaded onto MHC Class I molecules in ER - Complex transported to cell surface
36
Where is MHC Class II found?
On antigen presenting cells (APCs) such as dendritic cells, macrophages and B cells
37
What antigen doe MHC Class II present?
Exogenous antigens (bacterial or extracellular proteins)
38
What cells are MHC Class II recognised by?
CD4 and Helper T cells
39
What is the pathway of MHC Class II?
- Extracellular antigens are taken in and broken down in endosomes. - MHC class II molecules are made in the ER and bind to an invariant chain (Ii) to block early binding. - In endosomes, the invariant chain is broken down, leaving CLIP in the binding groove. - HLA-DM replaces CLIP with the antigen peptide. - The MHC-peptide complex is sent to the cell surface.
40
How is immunity to bacteria mainly achieved by?
Antibodies - Removing bacteria - Neutralisation and/or inactivation of toxins
41
How does the body remove bacteria that is introduced in low numbers or are weakly pathogenic?
Can be cleared by phagocytic cells alone
42
How does the body remove bacteria that are introduce in high numbers or are strongly pathogenic?
Induces an adaptive immune response
43
What is the immune response to fungal agents?
Innate immunity and adaptive immunity
44
What is a strong defence against fungi?
Phagocytosis
45
What pathway of complement can clear fungal infections?
Lectin pathway
46
What non-specific mechanisms are used in the immune response to viral agents?
* Induction of IFNα and IFNβ and activation of Natural Killer cells * Cytokines can be produced by macrophages, monocytes and fibroblasts * Cytokines induce an anti-viral state in surrounding cells * Cytokines also induce lytic activity in Natural Killer cells
47
What specific mechanisms are used in the immune response to viral agents?
* IgA prevents mucosal entry and re-infection * IgM, IgG and IgA prevent viral fusion to target cells * IgG enhances phagocytosis * IgM agglutinates viral particles * IgM and IgG activate the classical complement pathway * IFNγ has direct cytotoxic activity * Cytotoxic T cells kill virally infected cells * Natural Killer cells and macrophages kill infected cells
48
Immune response to Malaria
Infected mosquito injects sporozoites into the bloodstream. Sporozoites go to the liver, multiply, and release merozoites. Merozoites enter red blood cells, multiply, and damage them. Some merozoites become male and female gametocytes. A mosquito takes in gametocytes during a blood meal. In the mosquito’s gut, gametocytes form a zygote, then sporozoites. Sporozoites move to the mosquito’s salivary glands — cycle repeats.
49
Immune response involved in clearing malaria:
* Antibodies block invasion of sporozoites into liver cells * IFN-y and CD8 T cells inhibit parasite development in hepatocytes. * Antibodies block invasion of merozoites into RBC * NK cells are capable of directly killing parasitized cells, whether in the RBCs or hepatocytes by cytotoxicity

Immunopathology (13 decks)

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