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Immunology > Innate Immunity > Flashcards

Innate Immunity Flashcards

1
Q

Define Innate Immunity

A

Innate immunity is the 1st line of defence against invading pathogens.
It does not depend on previous exposure and has no specificity and no memory

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2
Q

3 components of innate immunity

A
  1. Physicochemical barriers
  2. Humeral components
  3. Cellular defence mechanisms
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3
Q

What are the physiochemical barriers of the innate immune system

A
  1. Skin
  2. mucus membranes
  3. cilia
  4. mucus
  5. HCL produced by stomach

Barrier that prevents microorganisms from entering the body.
Also includes high flow rates of urine, saliva, tears, mucus secretions from Resp tract etc

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4
Q

What are the humeral components of the innate immune system

A

After tissue injury occurs, a local inflammatory response occurs that includes the following features:
1. Dilatation and increased permeability of caps
2. Endothelial activation that facilitates adhesion of white cells
3. Attraction and activation of neutrophils and mononuclear cells.

The humeral components are
- Complement
- acute phase proteins
- proteolytic enzymes - lysozyme

Acute phase proteins and complements cause inflammation which increases blood flow and vascular permeability, and facilitates cellular responses (phagocyte migration)

All these responses are stimulated by vasodilator mediators such as bradykinin and histamine released from basophils and mast cells, and prostaglandin

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5
Q

Acute phase proteins

A

when an acute phase response occurs, acute phase proteins are produced.

  1. tissue injury
  2. release of cytokines (IL6, TF) by macrophages
  3. Production of acute phase proteins stimulated by cytokines, in the liver.

This facilitates defence and repair but the activation can be harmful when cytokine production becomes chronic

Acute Phase Proteins are plasma proteins such as CRP, fibronectin, alpha 1 antitrypsin and alpha 2 macro globulin. Produced by liver.
Involved in opsonisation and regulation of inflammatory mediators.

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6
Q

CRP

A

CRP is an acute phase protein and part of the innate immune system.
Produced by the liver
Release in response to tissue injury
Stimulated by cytokines (IL6 and TNF)
Binds components of bacterial cell walls and then activates the classical pathway of complement, independently of antibody.

During an acute infection of inflammatory process, the CRP concentrations rise rapidly.

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7
Q

Fibronectin

A

Is an acute phase protein and part of the innate immune system
Synthesised in the liver and released in response to tissue injury.
Release is stimulated by cytokines (IL6 and TNF) released from local macrophages
Binds bacteria and macrophages and monocytes, enhancing the clearance of these organisms.

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8
Q

Complement System
- Functions

A

Consist of a group of at least 25 plasma glycoproteins
- produced mainly by helaptocytes
- Activated in a cascade sequence
- w proenzymes that undergo proteolytic cleavage to their active forms

Functions:
1. antiinfective functions
- Opsonisation
- chemotaxis
- activation of neutrophils and mononuclear phagocytes
- lysis of bacteria and foreign cells

  1. Interplay between innate and adaptive immune systems
    - immunomodulation of b cell responses to specific antigen by binding to complement receptors on the b-cell surface. this results in enhancement of antibody response and immunological memory.
  2. Clearance
    - clearance of immune complexes
    - clearance of apoptotic cells via C1q , C3 and C4.
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9
Q

What is opsonisation

A

Coating the walls of bacteria so that they can attract and bind to phagocytic cells and easily ingested

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10
Q

Actions of the complement system:

A
  1. Activation of neurtrophils
  2. Chemotaxis.
  3. Increased permeability of BV
  4. Vasodilation
  5. Mast Cell degranulation
  6. Opsonisation -> phagocytosis -> lysis of bacteria
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11
Q

Activation of complement system

A

3 ways:
1. Classical pathway
- activated by immune complexes
- initiated by the binding of C1q to the Fc portion of immunoglobulin

  1. Alternative Pathway
    - occurs in the fluid phase, or on contact w foreign surfaces and is initiated by C3 activation
  2. Lectin pathway
    - initiated by mannose binding lectin (MBL) which binds to carbohydrate on bacteria and activates C4 and the classical pathway.
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12
Q

Activation of the Classical Pathway of the complement system

A
  1. IgM or IgG antibody binds to the bacterial antigen to form Ag-Ab complex.
  2. C1 molecules bind to the Fc region on the antibody.
  3. 2 or more C1 complexes bing the Fc region triggers a cascade of effects
  4. Outcome of which is formation of C3 convertase.
  5. C3 convertase converts C3 - C3a and C3b.
  6. C3 also produces C5a and C5b.
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13
Q

Function of C3a and C5a

A

C3a + C5a:
- cause inflammation and phagocyte recruitment.
- Causes SM contraction, histamine release and increased vascular permeability.

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14
Q

Function of C5b

A

Creation of MAC
C5b:
- Binds to C6 & C7, and then to C8 and C9.
- This creates the MAC - membrane attack complex.
- MAC = forms holes in cell membranes, resulting in cell lysis and death.

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15
Q

Functions of C1, C2 and C3

A

C1 and C2 form C3
All work as opsonins
Have chemotactic properties

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16
Q

Alternative Pathway Activation in the Complement system

A

Slow spontaneous reaction.

  1. Insoluble polysaccharides on non self cells + C3b
  2. Activation of alternative pathway
  3. Formation of C3 convertase
  4. C3 -> C3a and C3b
  5. C5 -> C5a and C5b.

C3a + C5a = inflammation, histamine, SM relaxation, etc

C3b + C5b + C6,7,8,9 = MAC.

17
Q

Activation of the lectin activation pathway in the complement system

A

Uses Mannose binding lectin (MLB), present in moderate concentrations in blood and tissues and produced mainly in liver.
Activates the classical pathway without the requirement of antibody.

  1. MLB binds to mannose in the carbohydrates found on the surface of many microorganisms.
  2. Bound MLB then binds to another protein - mannose binding protein associated serine proteas (MASP).
  3. MASP functions like convertase to cleave C3 proteins to C3 an and b. then c5a and b.

C3a and C5a = inflammation, histamine, SM relaxation, increased vascular permeability

C3b + C5b + C6,7,8,9 = MAC

18
Q

Lysozyme

A

Bactericidal enzyme secreted in saliva tears and mucus
Also present in neutrophils
breaks bonds in bacterial cell wall causing lysis

19
Q

What are the Cellular components of the innate immune system

A
  • Dendritic cells
  • Leukocytes
  • Mast Cells
  • Natural Killer Cells
20
Q

Leukocytes types

A
  1. Polymorphonuclear Neutrophils (62%)
  2. Polymorphonuclear eosinophils (2.3%)
  3. Polymorphonuclear basophils (0.4%)
  4. Monocytes (5%)
  5. Lymphocytes (30%)

3 Polymorphonuclear cells = granulocytes.

21
Q

Formation and function of granulocytes

A

Granulocytes = 3 Polymorphonuclear white cells - neutrophils, eosinophils and basophils.

Formation:
- Pluripotent stem cell -> Myeloid cells -> granulocyte precursor -> neutrophil, eosinophil or basophil

Function:
- Protect body against invading microorganisms by phagocytosis
- Neutrophils are main cell responsible for killing and removal of bacteria and fungi
- Eosinophils are main cell in multicellular parasites like worms.
- eosinophils bind to receptors for IgE (major anthelminthic antibody) and release toxic substances that cause swelling and detachment of helminth tegumental membrane and fragmentation and disruption of parasite

22
Q

Macrophages formation

A

Macrophages develop from monocytes produced in the bone marrow.

  1. Pluripotent stem cell - bone marrow
  2. mono blast - bone marrow
  3. Monocyte - circulation. Live for about 3 days.
  4. Monocyte crosses between the cap endo cells and enter the tissues and mature into macrophages.M
23
Q

Macrophage function

A
  1. Phagocytosis
  2. Breakdown of damaged tissue cells
  3. Processing of immune complexes by antigen presentation

Secrete a range of products including enzymes, interferons, IL, chemokines, TNF, NO, PGs platelet derived growth factor.

Antigen presentation with MHC class 2 receptor is recognised by the t lymphocyte.

24
Q

Dendritic Cells

A

Immature:
- Highly phagocytic
- express low levels of MHC
- When exposed to pathogens - triggers maturation

Mature:
- Abundant MHC and become APCs

25
Q

Natural Killer Cells

A

Have t lymphocyte morphology but do not possess the markers for B or T lymphocytes.

Contain cytoplasmic granules that contain destructive enzymes.

Recognise abnormal cells by:
- binding antibody coated targets
- receptor for MHC class 1 in viraus infected or cancer cells.

Important antiviral and anti tumour activity

26
Q

Mast Cells

A

Contain a large number of histamine granules
possess high affinity receptors for IgE

Activated by IgE, C3a and C5a

Activation = degranulation = histamine release

Effect of histamine release depends on site of mast cell
- Airways = SM contraction - bronchospasm
- Mucus membranes = nasal discharge, conjunctivitis, oedema, itching.

27
Q

List the Phases of the immediate immune response to infection

A
  1. Initiation of inflammatory response.
    - Neuts recruited and activated
    - Mast cells initiate inflammation by releasing pro-inflammatory mediators (histamine, leukotrienes, platelet activating factors)
  2. Adhesion molecules
    - Recruitment of phagocytes and lymphocytes to tissue damage cites involves cell surface adhesion molecules
    - these molecules allow the cells to move independently
    - the binding of adhesion molecules to their ligands = signal transduction which leads to cell activation
  3. Cell recruitment
    - Chemoattractants move cells towards the site of infection/damage.
    - FMLP from bacterial cell walls attracts neutrophils.
    - This results in other attractants from mast cell, macrophages, C5a from complement activation.
    - These chemicals all cause migration of neutrophils
  4. Phagocytosis and intracellular killing
    - Once neuts are recruited, phagocytosis occurs followed by intracellular killing.
    - Opsonisation facilitates this
    - Cytokines are released from a activated endothelia cells and Macs at the site
    - these stimulate the bone marrow to release more neuts into the circulation.
    - IL6 is produced and stimulates large amounts of compliment, CRP, MBL and Fibrinogens.

Immunology (4 decks)

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