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IMS LKC Year 1 > Immunology Part 1 LKC > Flashcards

Immunology Part 1 LKC Flashcards

1
Q

What is the immune system for?

A

To identify and eliminate harmful “non-self” microorganisms and toxins
To distinguish “self” from non-self proteins
Identify danger signals (inflammation)
Immunopathology

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2
Q

Principles?

Innate vs Adaptive

A

Broad Specificity vs Exisite Specificity

Minutes vs Days

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3
Q

Generation Times & Evolution?

Bacteria
Virus
Host

Polymorphic variable genes?

A

Minutes
Hours
Years
Host relies on flexible and rapid immune response

HLA and KIR control immune system, selected for by infectious diseases

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4
Q

Innate vs Acquired Immunity

1) Depends on?
2) Duration? Starting speed?
3) Specificity?
4) Cells involved
5) Soluble Factors Involved

A

Innate depends on pre-formed cells and molecules
Acquired depends on clonal selection, growth of T/B cells, release of antibodies selected for antigen specificity

Innate is fast (mins)
Acquired is slow (days)

Innate is limited - recognition of danger signals
Acquired is highly specific to foreign proteins ie: antigens

Innate involves Neutrophils, Macrophages, NK cells
Acquired involves T/B lymphocytes, Dendritic cells, Eosinophils, Basophils

Innate involves Acute-phase proteins, cytokines, complement.
Acquired soluble proteins are Antibodies.

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5
Q

Basic Principles of Immune responses and Timescales

A

Interferon (innate immunity) 1ST
NK cells (innate immunity) 2ND
Cytotoxic T lymphocytes (acquired immunity) END

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6
Q

General Surface Defences

Mech
Chem
Microbiological

A

Mechanical - Epithelial tight junctions, skin waterproofed by fatty secretions, social conditioning (washing)

Chemical - Fatty acids (skin), enzymes (lysozyme, saliva, sweat and tears) pepsin (gut), low PH (stomach, sweat), Antibacterial peptides

Microbiological - Flora competition for nutrients, production of antibacterial substances

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7
Q

Anatomical Barrier (3)

A

Skin - keeps out 95% of germs while intact
Mucus membrane in respiratory and GI tract traps microbes
Cilial propulsion on epithelia cleans lungs of invading microbes

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8
Q

Physiological barriers (5)

A 
Low PH
Secretion of lysozyme (tears)
Interferons
Anti-microbial peptides
Complement (lyses microorganisms
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9
Q

Cells as barrier

A

Eos, neutro, baso, NK

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10
Q

Cellular Mediators as barrier

A

Cytokine, Chemokines, complement, mast cells, secreted products

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11
Q

What is the acute inflammatory response?

A

Innate response to tissue damage.
Causes rise in body temp : fever response
Increased production of acute-phase proteins in liver.
1) C reactive protein
2) Serum amyloid protein
3) Mannan-binding lectin

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12
Q

C-reactive protein function
Serum amyloid protein function
Mannan-binding lectin function

A

C-reactive protein and serum amyloid protein bind to molecules on cell wall of some bacteria and fungi. PATTERN RECOGNITION
Mannan-binding lecin binds to mannose sugar molecules not often found on mammal cells
Non-specific, recruiting direct phagocytes (macrophages) to identify and ingest infectious agent

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13
Q

Cells of the Innate Immune System

A

Granular Leukocytes

NK cells
Identify and kill virus-infected and tumour cells
Recognize HLA molecule of virus-infected cell or tumour and kill them

Macrophages (mononuclear phagocytes)

  1. Garbage disposal
  2. Present foreign cells to immune system

Granulocytes

Neutrophils
Polymorphonuclear neutrophil : multi-lobed nucleus
50-70% of circulating WBC
Phagocytic

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14
Q

Cells of the Acquired Immune System

A

Granulocytes

Eosinophils
Bi-lobed nucleus
1-3% of circulating WBC
Required for immune response to parasites, helminths and allergic 
responses

Basophils
less than 1% of circulating WBC
Not Phagocytic - release granules containing histamines, serotonin, prostaglandins
Important in Th2 reponses -kickstarting acquired immune response

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15
Q

What does the innate immune response do? (4)

A

• Produce interleukins that activate inflammatory pathways (e.g. IL- 1b, IL-18)
• Elicits antiviral defence systems (e.g. type 1 interferon)
• Initiates complement and many other immune products to attempt to destroy the infectious pathogen
• Acts as the immune specific line of defence before the adaptive immune response gets a chance to be engaged

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16
Q

What triggers the innate response? (2)

A

Triggers of innate response
PAMPs – pathogen-associated molecular patterns
e.g. dsRNA in cytoplasm; bacterial cell wall components.
DAMPs – danger-associated molecular patterns
e.g. monosodium urate, high extracellular [ATP], reactive oxygen species (ROS).

Pattern-recognition receptors
Extracellular danger signals
TLRs – Toll-like receptors
Intracellular danger signals
NLRs – NOD-like receptors
RLRs - RIG-I-like receptors
AIM2

17
Q

What are some examples of adaptive immunity?

A

Examples of Adaptive Immunity
• T cells- such as CD8+, CD4+, CD3 and their products (e.g. cytokines) - cellular immunity
• B cells- such as Plasma cells, and memory B cells and their products (e.g. antibodies) -humoral immunity, CD19, Surface immunoglobulin class II MHC
• Antigen presenting cells (e.g. dendritic cells and macrophages) –these actually bridge the innate and adaptive immune response
Note: The innate immune system: buys time while the acquired immune system is mobilized, and helps to stimulates the acquired immune response

18
Q

What are antigens?

A

Antigens are glycoprotein molecules which react with antibodies or T cells. However not all antigens can induce an immune response in the host: those that can are termed immunogens

19
Q

What are antibodies?

A

Antibody molecules can be found in the blood stream and the body fluids and bind specifically to particular molecules termed antigens. They are the acquired component of the humoral immune response.The most basic antibody molecule is bivalent- with two antigen binding sites.

20
Q

Immunoglobins (5)

A

IgG
- 75% of our serum
- Crosses placenta, therefore important in protecting newborns
- Long serum hal-life
- Part of secondary immune response
- Bivalent- two identical antigen binding sites

IgM
- 10% of total serum Ig
- Complex of 5 linked bivalent monomeric antibodies, therefore 10 identical binding sites- multivalent
- Star-like shape
- Important in primary immune response
- Slightly lower affinity to antigens compared to IgG, which is compensated for by number of binding sites

IgA
- 2 basic monomers; dimer with secretory piece
- Found in body secretions, e.g. mucus membranes in GI tract
- Contains a secretory component which protects it from digestive enzymes

IgE
- Involved in allergic response and the response to helminths
- Binds to basophils and mast cells
- Triggers release of histamines

IgD
- Complete function not known

21
Q

What are chemokines?

A

• Small bioactive proteins that are secreted by cells that act to recruit or control the migration of other cells
• Four broad classes due to structure – CXC (E.g.
– CCR –C
– CX3C

22
Q

What is the basis of specificity of antigen?

A

Antibody’s binding site is complementary to the EPIPTOPE (region approx 6 amino acids long) on the antigen

23
Q

How does an antibody kill a virus? (4)

A
  1. Neutralization : Binds to the virus and prevents attachment to the cell
  2. Opsonisation: virus-antibody complex is recognised and phagocytosed by macrophage
  3. Complement- mediated lysis of enveloped viruses: cascade of enzymes in the blood which leads to the destruction of cell membranes, and the destruction of the viral envelope
  4. Antibody-dependant cell-mediated cytotoxicity (ADCC) mediated by NK-like cells (HLA molecule)
24
Q

Cells of the acquired immune system?

A

Lymphocyte
- Agranular leukocytes
- 20-40% of the circulating WBC
- 99% of the cells in lymphatic circulation

T (thymus-derived) cells
- Helper T cells: recognize antigen, help B cells to make antibodies and T cells to kill
- Cytotoxic T cells: poisonous to cells,kill cells infected by viruses and intracellular bacteria

B (bone marrow-derived) cells
- Make antibodies
- Have insoluble antigen-binding receptor on its surface. In fact have multiple clones of this receptor;
monoclonal antibodies

NK (natural killer) cells
Each subset has distinct cell-surface molecules, e.g. CD4 on helper T-cell which is the receptor for HIV molecules
Lymphocyte precursors are produced in the haematopoietic tissue in the bone marrow
T cells then transported to the thymus, where they undergo THYMAL EDUCATION, here 95-99% get destroyed as they have the potential to recognise host cells

25
Q

Describe the lymphocyte antigen receptors.

A

B cell antigen receptor : membrane-bound antibody, i.e. surface immunoglobulin which binds intact antigens; recognises surface of protein, therefore antigen must be in native conformation

Expressed on the T cell surface are 2 protein chains (alpha and beta) which together make the T cell antigen receptor (TCR). This binds to digested antigen fragments.

Each antigen receptor binds to an epitope on a different antigen, and is unique to a cell. There are many copies of the receptor on the cell surface

26
Q

What does the T-cell Antigen Receptor do?

A

Recognizes complex of antigen peptide and HLA (MHC) molecule
- HLA (Human leukocyte antigen) binds to little fragments of the pathogen, transports them to the surface so they can be recognized, e.g. so a virus cannot hide inside a host cell.
- Combination of short peptide from microorganism + HLA = recognition by TCR
- MHC denotes the Major Histocompatibility Complex (also known as HLA)

27
Q

How does clonal diversity occur in lymphocytes?

A

Random genetic recombinations occur among multiple copies of immnoglobulin genes (B Cells) or TCR genes (T-cells). Parallel genes undergo random Splicing and Recombination leading to large repetoire of antigen receptors.
Diversity of clones of lymphocytes, each clone specific to diff antigen.

28
Q

What is the primary immune response -clonal selection?

A

Antigen recognized in 1 out of 10^5 native T cells
98% in lymph circulation, 2% in blood
Antigen binds to surface receptor (IG or TCR) and causes selective expansion of that clone
Receptors binding with highest affinity to the antigen selected for, outcompete the rest, and proliferate to survive as the effector lymphocytes.

29
Q

What happens when antigen is removed?

A

Most lymphocytes die after fulfilling func.
Some survive as memory cells, epigenetically modified so next time host is infected, frequency of receptors will increase.

30
Q

How does immune response clear a pathogen? (2)

A

Cytotoxic T lymphocytes kill cells infected by viruses or intracellular bacteria. Recognises antigen peptide and HLA complex, releases granules of enzymes including proteases that digest DNA. Cell is destroyed - apoptosis.

Antibodies bind to pathogens, complex is destroyed or ingested by cells.

31
Q

How does a T cell meet its antigen?

A

Antigens taken up by antigen-presenting cells (take up particles, ingest them and present proteins on their surface)
Transported from tissues into secondary lymphoid organs, where they meet T cells
Initiation of acquired immune response
APC include B lymphocytes, macrophages, dendritic cells (best type, exist as immature DC in tissues, exists as mature DC in lymph nodes)

32
Q

What are the lymphoid organs?

A

Organized tissue in which lymphocytes interact with non lymphoid cells
 Sites of initiation and maturation of adaptive immune responses.
 Primary lymphoid organs produce the lymphocytes, e.g. bone marrow and thymus
 Secondary lymphoid organs include lymph nodes, spleen, and mucosa-associated lymphoid tissue
(MALT)

33
Q

How do lymphocytes move in the lymphatic system?

A

Lymphocytes and antigen-presenting cells circulate continuously blood and lymphatic vessels from tissues via lymph nodes/spleen into the blood

  • T cells spend around 1-2 hours in the blood, but the rest of the day in the lymph
  • The tissues are patrolled by lymphocytes, antibodies and antigen-presenting cells.
  • For example, the skin contains lymphatic vessels that drain into local lymph nodes.
  • Gut lymphoid tissue controls responses in the intestinal tract.
  • Antigens present in the blood are taken to the spleen.
34
Q

How does the immune system cause disease?

Immune deficiency
Overreaction to a non pathogenic
Recognition of self
Recognition of recipient

A

Persistent or fatal infections
Allergy
Autoimmune disease
Transplant Rejection

35
Q

What are cytokines?

A

Small proteins that carry messages from one cell to another

  • E.g. to stimulate activation or proliferation of lymphocytes
  • “kick-start”acquired immune response
  • Send messages to other cells, e.g. to kill or secrete

IMS LKC Year 1 (5 decks)

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