CD4 T-Cells: The Master Controllers of the Immune System

Question 1

where do CD4 cells develop?

Answer 1

Thymus :)

Question 2

which T cells are the conventional cells, which are unconventional?

Answer 2

• *conventional:** T helper cells (CD4+), Cytotoxic T cells (CD8+)
• *unconventional T cells:** NKT cells, intraepithelial lymphocytes, yg

Question 3

what happens to CD4+ cells in HIV infection ?

what happens after primary infection?

Answer 3

CD4+ progressively lost

• primary infection causes CD4+ to dip
• rise for a bit
• progressively decrease: clinical latency
• decrease lots after 4/5 years: opportunisitc infections: AIDS

Question 4

how do CD4+ cells recognise antigens?

what happens afterwards (differentation?)

Answer 4

• T cell has T cell receptor (TCR)
• Antigen presenting cell (APC) presents antigen to TCR via MHC-Class II molecule
• cell division: all have same TCR that can recognise same pathogen = activated CD4+ clonal expansion: turn into CD4+ Th0 cells:
• cytokines turn CD4+ Th0 cells into either:
• *1. CD4+ Th1 Cell**
• *2. CD4+ Th2 Cell**

as a result, make different products:

1. CD4+ Th1 Cell: IFN-y & TNFa
2. CD4+ Th2 Cell: IL-4, IL5, IL-13

Question 5

what do CD4+ Th1 Cell and CD4+ Th2 Cell make?

which type of immunity are they?^

Answer 5

1. CD4+ Th1 Cell: IFN-y & TNFa:
   - triggers cell mediated immunity (to target intracellular pathogens - see last lecture. using CD8+, NK & macrophages)
2. CD4+ Th2 Cell: **IL-4, IL5, IL-13:
   - **triggers humoral immunity (extracellular pathogens - B cells & lots of proteins)

Question 6

How do CD4+ Th1 cells help immunity?

Answer 6

(macrophages undergo pathogen phagocytosis)

• CD4+ Th1 Cells help macrophages: cause activated macrophages (kills bacteria and viruses)
• cell mediated immunity

Question 7

Th-1 response is neccesary to keep what type of infection under control?

Answer 7

TB !

CD4+ cells help the immune system to wall off the infected macrophages and bacteia - creates caseating granulomas

Question 8

how do CD4+ Th2 Cells help immunity/

Answer 8

• produce IL-4, IL-5, IL-13
• help B cells to make antibodies
• this drives humoral immunity

Question 9

how does CD4+ Th2 cell know which B cell to help? explain the mechansim xox

Answer 9

T-cell helper link recognition:

• dendritic cell takes up antigen, chops in smaller peptide and places onto **MHC-II
• CD4+cell recognises MHC-II, undergoes clonal expansion and differentiates intoCD4+ Th2** cell.
• CD4+ Th2 cell helps B cell to help make more specific antibodies
• B cell, when not activated has antibody on cell surface (B-cell receptor), binds the antigen directly, chops into smaller peptide and places onto **MHC-II
• CD4-Th2 cell** binds to (peptide-MHC-II & TCR) on BOTH the dendritic cell and B cell that have same antigen on MHC-II
• B cell makes then IgM, IgG etc

Question 10

what happens when b cells become activated?

Answer 10

b cells -> plasma cells -> make lots of antibodies (IgM, IgG, IgE, IgA)

Question 11

how do Th0 cells know whether to turn into Th1 / 2?

Answer 11

CD4+ Th0 cells turn into CD4+ Th2 Cells due to the prescence of IL-4 (itself is secreted by mast cells)

CD4+ Th0 cells turn into CD4+ Th1 Cells due to the prescence of IL-12 & IL-23 (secreted by dendritic cells, if seen bacteria and viruses due to pamps)

Question 12

what is the differential manifestations of leprosy for Tuberculoid Leprosy and Lepromatous leprosy ?

Answer 12

• *Tuberculoid Leprosy: limited disease**
• Th1 is dominant response: Cytokines IFN-y is involved
• activated macrophages
• low no. of organsims
• *Lepromatous leprosy: disseminated disease**
• Th-2 is dominant response: cytokines IL-4,-5,13
• high numbers of organisms

Question 13

what is the differential manifestations for cutaneous and viseceral Leishmaniasis?

and

TB?

Answer 13

Leishmaniasis:

• *- cutaneous Leishmaniasis:** limited disease: Th1 dominant response
• *- viseceral** Leishmaniasis: disseminated disease: Th2 dominant

TB:

• Lepromatous TB: Th1 dominant limited disease:
• *- Miliary TB:** Th2 dominant: disseminated disease:

Question 15

what is Th1 vs Th2 response to allergies?

Answer 15

• Th2 responses lead to IL-4, which leads to IgE, which causes allergies

Question 16

(need to know this less)

learn bits in bold

what are transcription factors for Th1 & th2 ?

what do - CD4+ iT-Reg Cell and CD4+ Th17 Cells do?

Answer 16

• T-bet is a transcription factor for CD4 Th1
• GATA-3 is a transcription factor for CD4 Th2

BUT:
also get
-CD4+ Th17 Cell: make IL-17 (know this one) defence extracellular bacteria
- CD4+ iT-Reg Cell: makes TGFbeta (supress immune response) immunosupression

Question 17

what happens to cells after initial infection has occured ? (immunological memory)

Answer 17

• after immune response, make a lot of effector cells (helper T cells, cytotoxic cells, B cells etc)
• dont have room to store all: most die
• generate memory cells:
• **memory cytotoxic T cells
• memory B cells**
• memory helper T cells
• long lived plasma cells: go to bone marrow and carry on producing small amounts of antibodies

stored for rapid deployment if infection reoccurs: QUICKER and BETTER response to pathogens encontered before